t THE UNIVERSITY OF KENTUCKY TOMOW Am MLTH RESLWH pw"M 302058483 BATCo document for Province of British Columbia 19 April 1999 TH6 UNIV M ITY OF KENTUCKY TOBACCO AND =LTII RESEARCH PROGRAM University of Kentucky Lexington, Kentucky P 77 q- February, 1969 ' 302058484 BATCo document for Province of British Columbia 19 April 1999 THE UNMRSITY OF KENTUCKY TOBACCO AND HFALT11 RESKARCH pRorRAM XNTRODUMOH AA The potential economic importance of tobacco to the atate of Kentucky A-r was recoenized by our predecessors at the University of Kentucky over fifty years ago. The tobacco research program was begun in 1920 and hug beea a ILI" i M h xt. T t pf mpry objective vas concerned very productive and fruittul e wiLh discase control and the culture of tobacco. An estimated 300 million dollars was saved farmers in the twenty years from 1935 to 1955 by findings of this research program. The need to expand the program was recognized by-k9th state and dAtio"I leaders in the early 1950's. This recognition led r to an appropriation of $50,000 by the Comhouwealth of kentucky f6f a atudyL that *as instrumental in the development of the National Tobacco Laboratory at ak Va-et of the $6 million Agricultural Science Center; congtiddtibn of a 0 million addition..to the Center-will begin in the sptir~g of 1968. In January, 1964.tbe "SiRokingmand-Health" report of the advisory. Couffnittes to the Surgeon CeM_Iral of the Public Heralth, Oery Ice was published.. -The report expressed, ~#e opinion that the association of smoking and health wAs -t.c- tot furth4i; r4a"rch was- togoized-by Congrods, and bearings i4ere biald to deterftine the most de$ b, Mealis of investAg4ting, this,~pmplex prc;'bl Rocognixing the Iaportan~ce of thAq problem.to~ society as a whole and to" Ke~ntucky in. particular 6o~ tfniverei' ~y of 1:4atutky. ev4luated -itA capability.for lu=lude~ now themical W agricuttural-lacience faeilities an& tho nutleus of thq atik(L required f4r s;'multidisciplinary approach to the proble'o. rRlloving the ORRR MR 4 1 t tu d Ex., john'W. owwald Preside& -of _,VnIvefilty YAntucky, 302058485 BATCO document for Province of British Columbia 19 April 1999 2 pl~dged to Congress the total resources of the University. Following this pledge, an appropriation of $1.5 million was made (1964) for smoking and- health rem~'-!t-h tM ho er'"Aj'PVAA At th., Kt-ftt(It+-' I!! teitihatnn, Kentucky. Later appropriations of $1.5 million for 1965 and $1.5 million for 1966 were made. However, a reduction of.$180,000 was made (December, 1967) in the-1966 portion of the university contracts associated with crops-research. In-addition, the University of Kentucky has invested over $250,000 for reno- vation-of laboratories for health related tobacco reoegireh. Facilities for tobhcco research now include-appro3timately 30,000 s4. ft. of net laboratoryj pace, one-half of which is used for aspects of health related f6bdafth knd Ovet 20r,&O sq. ft;,_bf gr6fthodsd ipaed for tobacco research. The replacement value of the facilities used for tobacco research at - the University of Kentucky am exceeds .$3 million. Future plans iftclude - facilities for the co"olidation of asstarciated phadeo of the proV". The annual bW&et totalS in exceds of $2.62 million for tobacco research of the '.University of Kentucky (AWndIx A) 302058486 BATCo document for Province of British Columbia 19 April 1999 DEVELOPMENT OF THE TOBACCO AND HEALTH PROGRAM Following the initial appropriation in 1964, the University mobilized its scientific talent and numerous meetings within.the UniversiLy were held to develop a tobacco and health program. The objective of the program was de- fined as follows: "to determine the nature and magnitude of the- relationship of smoking to health and, should a causal relationship be established, develop Wayu Lo lienLity alk-1 aliminaLe Lhe detrimental compounds". Our approach was 1) to concentrate on compounds considered suspect by previous iavestigators, 2) to develop methods to control these compounds (ie. breeding, culture, tobacco treatments, etc.), for all tobacco types, 3) to develop analytical capability to determine these and other com- pounds in-tobacco--leaf and.smoket 4) to discover teat systems to measure the effect an biologic .al properties of alterartions in owke com"sition, W to relaiti! the test gyllrtM Oith m6didal studies of' the response of humans to tobacco smoke. The program as developed represented the best thinking vithin the Aftiversity and was considered vell-balanced with,re,spect to the V-Umt. chemical and -pro meftcal xCie=es. 7~e, gram was -presentecf to the Agriculturfl Research Service V.-S. Depar"nt of A r1culture for ne*ot4ation- simM they w9ra to ppr approximately -$3DOMO is, eArmav)ted for AE*_$n-house, -$100,000 fvc AM-'admILnistrJk.% $i,,100,000 for contracta ith the Uni~rersity of' Kent' UC.kyl. -This 'fund Source is. limitod to res4i rch op n~xn-h~xmarL_*ubJ!cts. Thp fesearch,proposall P~rid by4n P~e iversity bf K4niuck y SciIMtJAts_ are %. IQVUwd md neg?tt&ted witlv.tha- P4ricult; al Re'. &rCh tervic UP 8.0 9. 1,;he first contracto,wer.0' 11~pqd b6catne offictia June 21, 1965--_ Ix I and Cfor Olt-90in -PM3*tt* X 302058487 BATCo document for Province of British Columbia 19 April 1999 4 PROGRESS The early stages of a new program of this magnitude entailed certain laboratory renovation, procurement of specialized scientific equipment and re- cruitment of a few highly trained scientists. The pKqgji~am 4as been underway .0 Znd one-helf yeArs and has developed into a productive interdisciplinary Fo r t- research effort. (See Apperidix D for research publications). The compaoition of tobacco smoke is a function of the comppsition of the tobacco leaf. Whole smoke is composed of the particulate phase and the gas phase. Whole smoke contains compounds that were present in the leaf in addition to compounds formed by the pyrolysis of the leaf. The control of compounds present in the- leaf, in order to control smoke composition, is the approach that in wing used by agricultural adienti6tt 6t the 11hilersity Of Kthtdeky. The present- tobacco and health rebearch effort Vag enh&hcod by fifty years of tobacc'o 'rescarch by the Kentucky Agricultural ;kptt-Imeht`StatI*h dciefitiffig. Research.on-all tobacco-types used.in cigarettes is included in the University 'of Kentucky program. Geneticists. plant physiologists and aoils scientists had,researc4 programs underway'~hat permitted rapid advancement in the biological. control of I-eaf constituents algog e~st4blishg.d lines. -The plant science stud"it, are concerned with the use of gettetics,affika cultural,practices to contrbl the subweances'.0'r precursorq substatie" ~n tobacco of .44cd in cijarettes ai~.being studied to -establish. the- quantities of s'petific con, irtitu"t$.Preaent and- the yariability'Anheren"n each. A survey 9~ over 150 F --odlections from- thi. world-adIl*eiriow. (robiwee An troduot4ons) =A varieti**. "in the U. S.'.has been'-tompleted ff4 js~~) The 'substantea presently under (A ppen luves lude~ t1 gation inc 'phenols",ffiterols., nitKosenoun Compo~%tds I luding'nicotine.:- nitr4bawinss,and ftco~bial toxins.- Y., '7~ ~~Ike i c~l' iii -k~, 302058488 BATCo document for Province of British Columbia 19 April 1999 the plant science prograin. The level of nicotine present in the leaf 19 Senetic.lly controlled as are some compounds that are suspect in the health related studies. A survey of tobacco introductions for quantitative differences 4 in phenol6, sterolr- noid cc:-,:-vc;unda hoo beett completed (Appendix B - 2, 4, 24 and D - 5, 6). A study on the influence of the environment in which tobacco grows (fertility, moisture, ete.-) on the quantitiea of plicuols, sterols and nitrogenous compounds present in the-tobacto I-eaf has also boen completed (Appendix B - 5, 21, 23 and D - 1, t, 10). An attempt is, being made to relite smokA composition to leaf composition and.to control leaf composition by genetic and cultural means. These studies will determine.how far plant science can go in the control of smoke composition. The limita of biblosical tbatrol must be studied[ and ident-Lfied. The chemists isolate and identify leaf and smoke constituents, develop analytical methods Ior their quantitative demifoin4tion abd -study - the influtfte that pyrolysis temperature has on thO co*o ition of tol6acco- smoke. The smoke chemists are measuring the variation in susp6ct dompounds when-the coal-. temper&ture-(temper&tureof burn) is varied. A-study inyolvi4 the.:r-hanges 'in levels of suspect compounds.in tobaccq condensate was recently completed (Appendix B~j 22 and D - 6, 9). variatlon_in-coal-ten~erartur& chanp3 -tb,e n._Tbbacdo smoke is'a very-compliex mixture and.thaswke cheMLita!'are gttwoting-~to.de~v6lpp Snalyii ftj4ues A .to futther. identify specific cb:Vo?nents (AppondixB 71, 9, 16 and I. An inter"tinS:and.e=WraSLU8 part of the Univers 41 sj~ftq~pqky -program actj~ tXejL -reaparch -1-aboratdry.' This l&b9rakpr3F 7.. -of fort,-Te~gtes to a14 tobacco and heala ribacarch' in.a rather" unique way.. ftesent chemi --3411 piermit,the 1"eltng or kadtotaw CaA techniqua of.' -4- 302058489 BATCo document for Province of British Columbia 19 April `1999 compounds present i1A the leaf. These compounds can then be followed through M-10 two pyrolysis (incomplete combustion process) and to the site of action in animal IM , Cells. Hopefully, this analytical laboratory would add resolution to the different studies across the broad tobacco and health research front (Appefid4v OM That part of smoke composition which makes up the tobacco smoke condensate is receiving major attention in the search for better bioassay techniques at the University of Kentucky. - The mouse-back tt-,.ae is the classical bio&ssay Lechnique being used to measure the biological activity of tobacco smoke. In the test. the mouse back Is shaved and smoke condensate is applied three times a week over a period of eighteen months (Appendix 9 - 11). The mouse- back test Is the best system available at the present time. Much time aftd ff t 6t th ! V ivti it f K i k d e i n or entac s t use y o in an effort to add precision y to the-bioassay system. The medical science program is directed toward-the search for sevexAl diffbrotit--systaft from single cell through organ culture including intact AnImAld that will interrelate biological action (Appendix D - 15, 20 and D - 24, 26, 27). The teatt shdulct be specific for several - nt smoke-compodtnts. differe The medical studies. inclu& les'earch to i 4 atify a component of the smoke that coul4 unmask a latent vims,if o ~ch exists. The suppositign that a spectftc smoke i~omponent wouldjmt _tM-V*JV1.iihrx1; 1 t wbW-d-=ISWAII~ In'tent virud which in'turn would,upset the call's regulatory system thus causing Oisaase. WOW& a"--14 01nd D 20 21 th 22) A h ff i i . no er researc e ort po nts toward the metabo , , Lsmof benzo(a)_pyreneI(a. clarcinagen) In,the animal. ThV possibility,eidits that compounds are brokefi-down into- ;CrActtona. or P10611~~~Jil;ii _Veswt with- bz i;;"ill ic& 11)i active tMn rM orl4inal qwp ourA (Appeidix~- n . . B 13, 0, 18 sjA D 23, 25). '-An electrop microscopic study 0(st 7 ZiZ7,5. 302058490 BATCo document for Province of British Columbia 19 April 1999 7 to identify tissue changes which occur prior to disease development is in progress (Appendix B-19). A study Lu determine the effect of whole smoke on the bronchiAl OpiPh-11i'm it undcz~way (AppeadiA B-17). Tile Lechniques to culture rat-tracheal rings are being developed. These techniques. if successful, would permit the identification of compounds that influence the ciliar J activity (Appendix B-12). J i rib 302058491 BATCo document for Province of British Columbia 19 April 1999 COOPERATIVE REIATIONS The University of Kentucky Tobacco and Health Research Program is coopera- tive with the-U. S. Department of Agriculture, Agricultural Research Service. The program desires cooperation with scientists in all laboratories interested in the problem. Communications are being established with research labora- torict in the U. S., Phg!-400~ FrArfc#s And Gormsmy. The frda -exchansa of informa- tion among scientists is fundamental to research progress. It is proposed that leaf stocks of cigarette tobaccos be developed to meet the needs of research people interested in samples for bioassay purposes. Particular attention must be given to known characteristics so that the re- sulting research-sample is the best that science and.technalogy can develop. At present, leaf stodke of loW-nicotint tobaccos are being developed to serve as a source of supply to competent scientists at the University of Kentucky and in cooperating 14kqrstories throughout the world. As our program yields research datg for the control of other leaf constLtWnts,- kampleA of leaf with biologically and/or phys-Loally. contra 1 led -composition will be- made available to qualified-,scientists for test purposes, ~,Predent the ejqep~iflc tdmirunity netds a reference 'or be reporting biologicalresponsfi to,tobacep condensate*'. We sErchgly recomimend th4t i"Irifeience c1gitetie'd' b6-ftrouiated by thood-intere-stat that would be used as. -a cont'rol in.~biologic#l'.experiments so that"'Iscicatists could'use it for compikring, the 4&ta. Much. co'n'fusion, AA repoTtLtka response dati- is,-,dw to Au Y. -ib encouraged. The ii6owladge of inikustiy iri both.'smok4.-chemistry'Aind Ui~ art phase of ttgarette mahufactur"s nwWed silace It reiatiei-to and'. P1Ays'a';*JorL role iii smekb coxpoditjott~ Dpersit ion of sci ~Mons i'11 Are4a *PC* 1.5 302058492 BATCo document for Province of British Columbia 19 April 1999 9 PUNS FOR THE FUTURE The complexity of the ausociation of tO~aCCG to hedlLh demanded a MUILidisciplinary approach Lu.Lho problem. To efvA bblalicc to tj Mll the decision was made to include from the beginning the plant, chemical and medical research areas. While it was recognized that avaiInble funds would not permit the development of numerous projects in all the disciplines, C"L would be taken to bcild fundamental knowledge in each area on which a total program could develop. Thud, theft-are notable weaknesses in Lhe program, especially in the--chemical and medical sciences. The chemical. studies on leaf and smoke are inadequate, however this area is be-Lag investigated in depth by industrial scientists. G66perstida at the technicai level with the- industrial scientists is necessary to gain both time and the available knowledge in seeking.a, scientific solution to. the questions beifig ask". CrOwth in tho medical sciences is recognized as the highest -pr6SrAtb ptiotity. The tlnl~ersity still feels- the importance of the- problem to the anoking public requires thaty4yo be found to -provide adequate,support for the needed ibedidal research.. Attempts are-being made to accomplish this objective. Based up?n strengths qnd weak- nesses oi ou- a presen t. research affOrt gur_program will d valoo in the.. -ftllew.inp; -areas Mofit -indicated an aisociatton, 1) .4pi#eviology. s"t*BticAl studies. two, etWe!tp tobacco and health but-the dature ihd saanito4e- of.'this association 'ify has. not been.estdblished.. *Iifareh~ appra'achas 8"king- to &oblate SO ideat ewii; otoer, faCtOrs which~ way be-iotpdrtant, e.&I pnetics,,swMas behavi 0 ljince~ any change In bioloilical activity mus't, be evaluated by epidemiological, atudies, pOrfettion of techniques thip area is a neceivit -No,.ptudiag at pregeat..,. 302058493 BATCo document for Province of British Columbia 19 April 1999 2) inhalatioit studies. Since natural human exposure to smoke occurs through the bronchial tree there 0% need for increased researcb-or such. Correlation with other bioassay systems is needed. No studies at present. 10 3) Special biological tests. Although the conclusive test must invoLve whole smoke, &woke is so cciaplcx that specific bi,?1,)-Lcal testa to resolve effects of specific components is necessary. increase needed. 4) Mechaniams of amoke generation. Fundamental studies am needed for a more complete understanding of the mechanics of the smoking process and its effect upon smoke composition. No studies At prescnt. 5) Chemical studies on tobacco and tobacco smoke. Expansion in needed and it would be desirable to cooperate with industrial scientists. Inc~rease needed. 6) Filtration. Selective filtration studies must begin also in concert with industrial scientists. No studies at present. 7) Tobacco treatments, Techniques to alter coal temperatures andlor smoke compositibn sndbld be expanded. ~emqval of proven 8),,,Pjant~_K~e.nce research.. Studies for. bio~pgical jj harmful or enhancement of beneficial constituents should be-ex'panded. of 00 It would also seem esafttial, for pL deftaitak or the magnitude -smok$.ng and health problem and for meaningful scientific re"Arch, that greater aftetititt `~b6 parid to -tho -sk*Jew ua*d-ta r*66acck. 4P6C41_9j4aVettes_ ith, -will requi e kaoopir t ive. known _-tiharac%teristica in each ofthe tobacco types r a iffart )between the University and-industrial ~~fenttstsi workW&LWtth tigireite Wk s.,,--h-ievtr 1 46Q*M~~ftot Onlylo tbe univer iiy -of K"tucky program, bUtL &lsor to other smoking and heilth peograms.in the' ~7 I United State# io throughout the vorld'. it iv envislatked-that the initisi, DOOM a4tablish 'a sound base for fti~rv'ntudiea inVolving filtration i" ap. f t i-*w, 302058494 BATCO document for Province of British Columbia 19 April 1999 A" Present chentical studies of tobacco and smoke are inadequate and would profiL greatly from a cooperative technical effort between University and industry. scientists who have considerablt! er.P-L1L- Li thin. 4rr:5. The present biological testing effort is significant and much progress is being made in the development of specializcd tests tif fut"re importance. T However, the present faciliLies are wholly inadequate for the volume of samples that must be anticipated when the program becomes fully effective. It is con- sidered easenLial to start planning for this eff-urt. it would Seem that epidemiological studies must evaluate any changes made in the biological activity of smoke. Present techniques have not fully con- oLdered interaction Of tffibking vith auch factors. as genetics, air pollution, and AAsuf fic tent attention-has been paid to the smoking behavior of individuals. Ilerfection of epidemi6lftlesl -tddhniques is consideted to bd absolutely essential and work in thi-,area must be expanded. With these thoughts in minds the University proposes the followids po a it iv e. Steps:. 1) the'Univermity will assume. res pcps ~bri lity for.the estatLlishment of 00, procedures for the,pj~pductioa Of'a refeVence- cigarette whiah can be used in,lany medic*al. risse rch pr~gvam ks. a--r&feeonce. polut',. -relations wilLb 9 0 otfier solenti t t produce' spi~c~lal samples'with known cherectari4tics which-afe needed 'to answer spicific questions of medical- iriterest, ttm University villa xtxiva. J9r c4~operation w Itb A) other 6baoco researeh pibgramst. ._,~).cuippany scientists at.the technical laved, atfi~7r sm'kirts ohd h6alth program$ In the United Stotea~abd abroad. 302058495 BATCO document for Province of British Columbia 19 April 1999 4) define medical problems and develop proposals which, with the help of experts. can be submitted to variotiB granting agencies for their consideration. Define the future needs for adequate biological LebLiUS 5) establish a scientific advisory board which will provide advice to the University of Kentucky Tobacco and Health Research Program. BATCO document for Province of British Columbia 19 April 1999 302058496 StR4MRY The University of Kentucky Tobacco and Health Rescarch Program has been underway for two and one-half years. It is a university-wide effort involving Lhirt7-ti~K Af'40"Vistg in four colleges of the University of Dntucky. The program is multidisciplinary and includes major efforts in the plant, chemical and medical sciences on the campus at the Uiiiversity. Cuucdinatium and cam- munication. among scientists with widely differing interests is encouraging. The studies encompass the biological C011LIC.1 A_C0nCt!tttefttR Ity tile leaf, the cbemital ehAriges in compounds that occur during pyrolysis and how the whole smoke composition influences the animal cell. Significant accomplishments of the tobacco and health research effort reported to ddte aft 1) that polyphenols in tobacco leaf can be lowered by genetic contr OL 2) that the quantity of sterols in tobacco (14. tabacuth) is quite amalli J the_ genetic variability is -leat than- expected, 3) that certain chemical compounds when adde'd to to'bacco wil7l alter-burn tedipetature and result in significant changes in the quantity of suspected health-reldted &ompounds in the smoke, .4) that amino acids present in-the.leaf vould yield polinuclear, -aramatic hydrocarbons when pyrolysed-~-pozsible g6oetic cofttrol needs, addUional inventigqLtion, the suciessful, culturirtg',-of t-racheal rLn$s of -rat Clou fd be, quite usitu 6) that the -inl~ettigaZi soxb g characteristic ft-0ith,'felatos tde-baaad in td-t1he pkerselko-df, &-latenX. further - inve tigation ko-det"ine its significance -to this"~ 1-ims 7) that over twenty-iAve. scientific -re.oeareh papers~ have resulted Irpm the -tofiadco and..health researcli effoiv. to, the total biol~ogical_ippraack- On one 'toe 410pu _Xecide the d iplineg to i6n46rtske.s0Akq,pr*grayL." Th*~University enviroamat-makes posaible the coarmMication. with &Ad &M.Ps illecientists yJh ore tm" -in the ti~~acw, ;p h -o'~dte h"Ith t 302058497 BATCO document for Province Of BritiSh Columbia 19 April 1999 App,~ztil. A A TOBACCO AND IXALTH BUKEET Annual i ti a appropr ona for tobacco research at the University of Kentucky total $2.2 million of which $1.5 million is health related. The U. S. DeparLmnt of Agriculture administers the $1.5 million appropriation. Appra-iinatcly $100,000 is charged aG ra.~,aLuistrative overhead by the U. S. Department of Agriculture and approximately $300,000 is for support of tobacco ' and h lth h b A i a researc y RS v t' I= o-hmiso -t-titis -4 -atcd at tt.~L Ukkivu,.siLy Ur Kentucky. The remainder of about $1,100,000 is negotiated by ARS with the University of Kentucky for contract research through Eastern UtiliZaLion Division, Crops Research Division and the Marketing Division as shown below. Numbers in parentheses Fefer to the number of contracts and cooperative agreements. Annual Support for Tobacco and Health Research from USDA-ARS Source* Contracts and Cooperativd Agreements 1965 Plant Science (4) EVD JgT TOTAL ' 45.T00 34275& Chemica.1 ScUnce. (3) 262~031 ..0 0 031-' 262 Medical Science (6). 52,4, 0 , 524 593 Coop. Agreements (4 91,500 ~53, OW 0 , 244.500 . 1" 373, 674 Pl ' ant Sgience _(4) 0 -.280 473 127 - 40 L 330 0 mmical Science, ID - .521.969 ' Medieil Science 4) ~ -231,1.16 `0 ~O 231,116 -7 Coop. A#reeiten~419 4) 911.959 209~i 1 IS 0- 308.077 - 1,40,500. ontracts And Coft ratLve. A~ reemen~s ~7" .'0 (4) 27 71,!W3 89 i 020 366 921 CheMLcal-Scienct- ' (3) Z32,969 1 ...G 0 , :232,969 Medical kience (6). 454.693 .0 454 693 IS 900.', 215,300 0 , 31 t ~00 1, 365,18 S %%wed 302058498 BATCO document for Province of British Columbia 19 April 1999 Appendix U UNIVERSITY OF KENTUCKY TOBACCO AND HEALTH Elant Science RESEARCH PERSONNEL AND PROJECTS I. Bush, L. P., A~st. Prof. of Agronomy Specialty: rlanL physiology (seed physiology) Hiatt, A. J., Assoc. Prof. of Agronomy Specialty: Plant- metabolLs" midt-eal tiuLX-iLion of plants Pr?,Jr-ct: luvestigations designed to study the biosynthetic and metabolic pathways of secondary amines and other aiLrogeft compounds and to observe the translocation and redistribution in tobacco plarits of health-related compounds and means of regulation of those compounds. $112,829 Z Davis, D. L., Asst. Prof. of Agronomy Specialty: Physiological genetics Project: Tobacco and Malth related resdarch-iftolving genetic control of sterdis and nitrogenous constituents. $ 74,656 3. Keller, C. J., Asst. Prof. of Agronomy Specialty: Plant physiology and biochemistry Grunwald, C., Aust. Prof. of Agronomy Specialty: Steroid metabolism, plant growth regulators, ion uptake Project: Tnvestigations designed to study the metabolic processes of certain. compounds.. Luc lud-ing nitrogen bases, sterols,, pbeftolic compounds. and isoprerlo-ids in tobacco plants. from green to post- harvest stages and 6ethods of. regulation important to sooking and health reiated -problems., $124,808 41. Sheen,, S~ J. Asst. Prof.- 'of Agronamy specialty:' ftsioloocal. genetic-6 - AW ra- -rel i Project: Cen~tlc stitdies on the igboift-l" nf-mI3~p ito 9 9t as to wkir~f Bad -hee4- segregatiuj gener#tAoiis of tobi~6. Sins, J. I., As;t~ -POX. a f- Ak"%W~rO' -Brooteten. i. 3, , Asst. Prof. of Asronomy esialty: 'Nitrojen trarisformatioh in soils; mii;iob W i41, P~vl;e.ss*& J in. 961-14-Z nitij...%ariiiprk 'ofplants" rct 'Inve4t1gatif d to determine the ftlatioi3 --of ~ps deoigne acco aitrageft mtrition oftob ev an:d to 4 glop, infaimaei~rr P~( ~A_ aii4 other urtfavkrabla. orgapic.,coastituenita' in. the tobacoa,plant. -and health rk!1a4*d.rqsearch -on the-effeats.of Ptojogt: ~,Tobarmo agroAdmic fadEors atW growth. reju'lators.on cer.tain hPalth-r.elated compounds in burley t~bac~*. 69,267 Projei~t: InvostigatIvAN163iined 0-.s.tu4y tht effdk",~f V& ortil~zqr, ~aulturAa praq;tic . , 302058499 BATCO document for Province of BritiSh Columbia 19 April 1999 16 6. Yang, C. Y., Asst. Praf. of Plant Pachology Specialty: Fungai physiulogy, soil microbiology and electron microscopy Project: Investigations on the carcinogenic and other toxic weLabolites produced by tobacco fungal flora. $ 89,020 ProjVCt: Investigations on the effect of foliage micruflora arui viruses on compositiun of $ 45,000 Rr,Aject. Livestigations on the rile of microbial activity in producing carcinogens in market tobacco. $127,865 Chemical Science 7. Brown, E. V., Prof. and Chairman, Dep-Arrnpnt of Cliemistry Spoeizilty: Oa:ganic chemistry - reaction mechanisms, heterocyclic chemistry, carcinogenesis Project: Investigations.-of nitrosamines in cigarette smoke. 86,323 Project: Investigations of the chemical composition of the heterocyclic bases in cigarette smoke. $ 71,465 Project: investigations on the isolation and identification of the higher boiling heterocyclic nitrogen.compounds of ci arette smoke. $ Green, J. G. , Assoc. Prof. of Agronomy Specialty: Experimental analytical biochemistry, instrumentation development, and sub-celJolaie physiology -Projvct: Investig4tions on ihe. analysis of tobacco,,tobacco smoke and fractions thereof' $311,394 PrOje6e, ravestigation; on the manufacture of experimental cigatettes and the preparation of.cigarette smoke conclezlWe. $123,731 4 Patterson J. M., Prof. of.Chemistry C Sptcialty: Organic chemis try chqx"try -of. 4a teracyc c ca~666~ds, 'i~iiro coq,)oupda, high twoperatuire, -react ions an4,phot*cbemlcs1 reactions Smith~ W. T., Jr., Prof. of Chow stry-... -Specialty: -'er0ac Zh~Riat_ry IAZ oyet (P S"44d h emperature reactf4ns~, Uibsiisatlons an the -chemical compolition.of,tho pytolyttic. PUts ~Pf Amin" ac!4a.- -Offtet~f t~iial.vkriitionv. an' :-P-Jact: -Ilaveq 4 a C a tion, OL apino acid:pyrolysated'. 10. Zaw, Asst. Pr'f. -of Airo' "0. eno Lea, 'too" identtff~ tion 401. t ~Xnvestlg, krojec 'i ttiqns ock t he deve ~vpmq~nt ~#q JiWrav6d,.,M#ft6~v foe d1e ;i ko- .41,19, 107 --:-i6jectl -IT~Vvstigativas. .00- thi 4ev4pp;aent of an lmpro,~-ed ,Aavilytlial *thpd fcvr. dais rm4dvS pp lynac Isar - a"dt.,ic hy.4racarbow and..h~etergi-. -eye. Its.. lie cwVaw4q 4nv1gerette Soo 77 1.6, 302058500 BATCO document for Province of British Columbia 19 April `1999 17 Medical Sciences il. Braunstein, H., Assoc. Prof. of Pathology Yoneyama, T., Asat. Prof. of Pathology Specialty: Lung diseasc, haematology Project: in-uestigatioas on the biological assaying of various tobaccos, smoki, condensates, and rclatcd substances Cux carcinugeuic, cocarcinogenic, and related activities. - $110,773 $ 96,814 12. DonneLly, G., Instructor of Cell Biology Specialty: Mitotic phenomena, cell division phenomena Permn, k. , Assoc. Prof. of Medicine Specialty: Pulmonary physiology Am"im 4 o Project: Investigations on the development of new techniques for biological evaluation of physiologically active substances in - tobacco leaf and smoke. $ 53,681 Project: Investigations on the effec 't of tobacco smoke constituents- on rodent tracheAl. -rings gr9wu in tiosua culturO. $ -83~ 186 13. -Flesher, J. W., Asst. Prof. of Pharmacology fipecialty: Biochemistry, pharmacology Project: Investigations an the distribution-aad metabblism of. benzo(a)pyrene. $ 64,166 14. Hunphrey, L. J., Assoc. Prof. of Surgery and Cell Biology Specialty: Iftnunology of carcinogenesis 'Project: Cellular mechanisms of aarcinogenesis., $ 84.471-. Proj4ct': Investtgations on the'response of Viru3~-cell culture Sys teAs to tobacco smoke con4emate and fr*tzibnt_- $ 13,2.69 15' Lalonde E. Asst. Prof., of Oral Pathplo 9 y Specialty:` -Oral p&tho,"gy, -oral abOorptlon, Protect: on arni carcirRgenesIt In hd4viLeks-'. Projer-t! GrAl. abarorption and saliva. $.79,79p' -6 Pr -f i4i&lc rl~ ROAU,-, Ab d6 of.. 0 Mandelqtam. F. I ks,"O. Prof-of Medicine -OSpecialty: GAstroenterol9gy, biochemistry, cancer Project: , "InVA!Siiset tons on Xbe absorption of-. 6arcluagaus s4 ==turiL1li-,xe,4ked noncarcli~pge a fr6m-tfie. gabtroUkte4t1n&k tr Qt of rodents. '$6.500, id 1,,. .Roecko-li. T., Assoc. Pfof. -of Patho,'argy Speqalty~,'PathoAogy ci Il- tur~ovqr. ?Koject- IavetUgax~ons qn respir~~oxy japithelial -361 is. sydnor, K.,'Ass". ProX. of Medici=' 302058501 BATCo document for Province of British Columbia 19 April 1999 19. Weiss, D. L. , Prof. of ratixjogy Specialty: Pathology Project: Investigations on the determination of the effects of combinations of cigarette sutoke and nononcogenic viruses an the development of lung tumors in rodentH. $112;.679 Project: InvesLigationg 00 the of new techniques, for bioiogical evaluation of physiologically active substances in tobacco leaf and smokc7 S117 ~ ..739 20 ~ White, D. C., Assoc. Prof. of Biochemistry Specialty: Electron transport, phospholipid metabolism Project- Investigations on the electron transport system.of Bacteriodes piplaninopen~,--s. 66,083 Cooperative Aereements 21. Andersen, R. A. , Asst. Prof. (Adjunct) of Agronomy Specialty: Biochemical research Project: Studies of phenolic compounds in tobacco. 22. Benner, J. F,, Asit-~ Prof. of Agroq6my Surdia, D., MiNt. Prof. CAdjunct) of Agronomy Burton, H. R., Asst. Prof. of Agronomy Specialty: Orgatift -analysis, tobacco and tobacco smoke Project: Development and-evaluation . . . L of Cigarette twdifiers which' _0 alter smoke- compositio'n. 23. Cheng, A. L. S. , Asst. Prof. (Adjunct) of Agronomy. Specialty- Lipid metabolism& Project;. Investigatiorti on the'leolation and identiftcation of the higher boi.ling heterocyclic ni-trqgen compounds, of,,cigfi~e~"_ huWm.. Legg,' P.' D., "at 'Prof. (Adjt~nct). of.Agronoiay Specialty: Quantitative genetice,and biometrics Project: Spadi s.: on the inlwritaioe of import&A c&~i~tertstics in 'tobacco.. 0 .7 _ 7 ~A. 302058502 BATCO document for Province of British Columbia 19 April 1999 19 J Appendix C OTHER UNIVERSITY OF KENTUCKY RESEARCH PROJECTS WHICH RELATE TO THE TOBACCO AND HEALTH RESEARcH PROGRAm 1. Flesher, J. W. nppt. o" Pharmacology Carcinogens and-mauw"fy cai,er. Spunsoring Agency: Anw-rican Cancer Society 2. Humphrey L. I. , Dept. of Surgery 6, Cell Biology The effect of stress on the immune response of normal and tumor-bearing animals. Sponsorin enc A A i mer y: g g can Cancer Society 3. Fatt,:!i&on, J. M. Dept. of Chemistry High temperature reactions of substituted rroles . py Sponsoring Agency! Army Research Office - Durham 4. Penman, R. W. Dept. of Medicine Chronic lung disease structure analysis. Sponsoring Agency: National Institute of Health 5. -Effects of cigarette smoking 0im ifittapulmonary ventilation perfulrioh relationships. Sponsoring Agency: American Medical Association 6. Rees, E. D. Dept. Of Medicine 0, Develoronent.of perdictive test of hormona deperido-ney in 1 . experimental m1dimary tancer. S ponsoring Agency: American Cancer Society 7. ..Karotypes of.-rat$ fran strains of,.differeat *usceptibility to maugnary cancer induction . Spqnsorii~g Agency; -American Madt"r Association _ L L 8. T&ite, D. C. -,Dept., of Biochemistry Cytochrome ox~daies_ln bagteria. 5 ~aisoFLug Agency: NatAon-l -Sate"i-sow-dicift r, 1 7 ~ , "i 302058503 BATCO document for Province of BritiSh Columbia 19 April 1999 20 Appendix D PUBLICATIONS FROM THE UNIVERSITY OF KENTUCKY TOBACCO AND 11EAIMI RESEARCH PROGRM Plant Science 1. Atkinson, W.O., Ragland, J.L.; Sims, J.L. and Bloomfield, D.j. The influence of irrigation on the responses of burley tobacco to nicrogen-fertilization. (Submitted for publication). J - - -1 2. dush, L.P. Succinyl thiokinase of tobacco, Apt-6homy Abs. (Abstract) Nov- 5-10:24, 17-57. 3. Grunwald, C. J AM The effect of sterols on the permeability of alcohal~treated i U red beet t ss e. Plant Physiol, in press, 1968. 4. Reneau, R.E.; Ragland, J.L. and Atkinson, W.O. !L Effects of ammonium nitrate and the growth of burley tobAtco plants on soil p"SuMitted for publIc"Ation). 5. Sheen, S.J.; Calvert, J. and Stokes, C.W. A A survey of chemical constituents in cultivars of Nicotiana Labacum from different geographical areAn. (Submitted for .W publication). 6. Sheen, 9.J. and tLokes , G.~_ Polyphenol variation in seven Xy iso lines,.of- tobacco. - Aptronomy Abs. (Abstract) Nov. 5-10-1-9. 1961.- Chemical Science 7. Andersen, R.A. -and Sovers, J. ..OptiTmm condit4ons far.boadA-ag -of- plant-obdiable to insoluble? i*iyt6ch,6m. $z -are polyvinylpyrrolidone. J.IP,. Buftoh. H.R. and BurdIck.- D. -CLzirettt '"Oka from-fiieh-qnd -low-attrace burl Compos,itionof tobaeLo;' ud 9. BurtaAl II.R.. and Burdick-D.,' Thermal decoff"~&~tiqn *C(obaczo -I.. Ttiekmo grayisetric-anaVois. Tobatco7 SCt.'. X1 Iso- 10~'. 1967. 10. Cheng,'A. e Cured tobw:co varieties. -Tabacc in ipress, r 11, Patterson, J.M.; Tzamasfyros, A.- and Smith-, '14T.' Jr. J, Pyrolysts of pyrroles. .(in zaautcrij~r,). 02058504 3 BATCO document for Province of BritiSh Columbia 19 April 1999 21 12. Zane, A. Determination of anthracene and pyrene in cigarette smoke by gas chromatography. (Submitted ror publication). 13. Zane, A. DeLermination of phenathrene in cigarette smoke by gas chromato- raphy. (in manuscript). 9 Medical Sciences 14. Courant, P.R. and White, D.C. Formation of an electron transeperr -iyrftam ii. naCLeriodes tuclwinogenicus Bact. Proc. (Abstract) 1967:105, 1967. 15, Flesher, J.W. DistrIbution of radioactivity in the tissues of rats after oral b administration of 7,12-dimechylbenz(a) anthrar-ent-3 H. Biochem. ii Pharmacol. 16:1821-1831, 1967. 16. Frerman, F.E. and White, D.C. Membrane lipid changto during formatioa of a futwtionil electron transport sy tem ih Staiihylococcus aureus. J. Racteriol. 94,6:1868-1907, 1967- 17. Humphrey, L.J. Immunologic -studies on the hemadsorbing factor of malignant-tow"zi Surg. Forum 18;94# 1967, 18. -Humphrey, L.J. Studiqs on passage of- -the howdsorbfng factor of muriqe. tumors to normal call cultures. Cancer Re.s. In press, 1563.... -19. Humphrey, -L.J.' onship of heinodsorption Studies on the reliti ~y normal murin4_splew. And'murine tumors. -Cancer &a i pre-s,,1968. _s, n a Xem~dsorbitxg "factor af. lis~=e tumors. S Ma 12!4% 16 106 21. Humph e F. ; `Tan"f, 4. _a~a__kite'bsky..E., ~emadsorption.,by murine twaors'. Fed &oc_ (Abs act) 26:102, _L967. 22. Humphrey, L. 1. MtlgrQm, F:; Tonder, 0.'. and.-ffirebsk3~~ He6dr-orption by. r~u~~ne tumors- jn_t.'ArcIf.- Allergy 30-474 19 6. 23- Rees _71 ted "do of 'raz'Amall, intoWn Fed '(A st' Mona bk,ever Pqc. ratt), in ipress, 1968. 24 t kt~zza, V.; -Sinclair,, P.R., Atte., D.C. and Courant,, -P.R. The electIon *trAq#sport system of 4.acterlodem malaninogo'nit1w. (~,qbi4tted -for iublication). 302058505 BATCo document for Province of British Columbia 19 April 1999 -z- -- A. .'~- X_ 25. Sydnor, and Flesher. j W. 22 CImParaLi blo'OP""l P,Itcncy of met"bOlites Of--DMBA. (Sub-nitted C., Pu~licatlon). 26, Mlitc, D.C. Changes in plicisphol CICCtron transport ay-em. and tile mW'fjc':_." ul the 27. jr__0c- (AbSLract) 26:3378, 1967. Whit-, D.C. and ler,:,an Fatty acid c___!. F.E. _...'_-Eion of the comPles lipids Of starhylococcus -au_reus during the formation of the Inembrane-bound electron trAnitPOrL "Y""n" (Submitted for publication). ~7. ji T 7 _ "-41 302058506 13 ATCO document for Province of British Columbia 19 April 1999 I Appvndix E TOBACCO AND HEALTH RLSEARCH PROGRAM Program Dircczor - G. W_ Stoker, Plant Scienct. Atkinson, W- G. (Agrop) Bloomfield, B- J. (Agron) jirrh, 7.. F. (Agron) Davis, D. L. (Agron) Grunwald, Claus (Agron) Hiatt, A. J. (Agron) Legg, Paul* (Agron) Sheen, S. J_ (Agron) Malcolm (11. P.) M,0ic,%1,ScJenr-- 23 Anderson, R. A.* (Agron) Braunstein, H. (Path) Benner, J. F. (Agron) Donnelly, Grace (C. Bio!) Brown, E. V. (Chem) Burdick, Donald* (Agron) burtOILW H. R. (Agroft) Chong, Amber* (Agroti) Green, J... G. (Agron) Patterson,' X. (CtUft) Flesher, J. W. (Pharm) Humphrey, LuLeu Lalonde, E. R. (Oral P.) Mandelstam, Paul (Med) Penman,.Robert (Med) Rae&,, Ei D. (Med) Siegel, Smith, W. T. (C4gm) Roeckel, Irene (Path) Sims, J. L. (Agron) Zane, Alexis _(4grARj Sy4nor, Katherine (Red) Van Meter, Carol (Agron) _. Weiss,_D. L. (Path) Williams , J. C. (Agroa), ' Vhite~ David (Biothem) . 'P.) yongi C. Y, (P Ya"yUma, Tetsuo (Path) C, aeco.an& Health: Tobacco and Itealth TobiKcco and Real-th , Folley Compittee Tedmital -C~i t tee- Ri~aseay ~Ouncil C Albright. L. D. M~ec. V. P. a r F~ Ae " txVi P. -Roo i Coc r&, Gtie~n -(Agron) ~ saidiek, Wttalo (Agtait) ' , Nagel, P#Ul' C. (Dean-AW ~Pot'tersani, J, M.. (Chent) Gi*eu~ J. 0. (A'gr;4'' 7. ~eayr Rig 11and. J. L., _ (Agron)' Soilth,- W. , Folp, 0, L. (Path -y*Uz` z- -Y.: (r. P.) Yang;., -c. Y (P. P.), 302058507 BATCO document for Province of BritiSh Columbia 19 April 1999