N- I !,.,i 11 0,04 V L`;L. FU I IUL jnj~: rcpurL j', to revil i,xawii.-- -tid pro.it rilw a9i 4,11i. In .I 1010:-'t, O'l I L-t.~ f0.iAn,j tu tob,)Cc :A-1lU i F-1~ -11d 110JI LUcLiiiining it) 0,11. activitil.,; and filldirrs, can 1), vi-bitrat,11, divide(; ittt,~ 5-ycar 72rioft. Thc first or'- -..-cond -,:-iod,, cov:-. thc pcist and pvcscnt activities, while thc third pciri6id projCcts out- fi-t-a-e plaris ill developing a safcr tobacco. 1964-1968 - Exploration period 1969-1973 - Experimenting period 1971-1978 - Dcvcloping p--riod At each period we enjoyed the co~,p~~i-ation fiv,t NCI and many scientists f rom 41-his Group. In 1964-196G, Drs. Kotin and ral?. from NCI took active parL in the conception of the ARS tobacco-health progrz.-,i. Now many scientists ill this Working Group are collaborating or participating in our research. The- etivities which I am. going to describa "include IM Intra- and extramural ch a~ tie] I as cooperati ve efforts wi th -don-esti c and forei gn nsti tutas .resear When t.he Surgeon General's Report-on Smoking and Health was released in 1964, plant sci6htists we-re uncertain as to how to modify the tobacco, plant to meet the, Aieed- One cool d not ~ist-inqui sh', front them haill-th point - of viml, which sample is more desirable than tM other, and there was-no -7,7.7 302058799 BATCo document for Province of British Columbia 19 April 1999 7777 for I\, j w, di I i i,y t%,n.-, io, I C.,.f,i 4.1 -i I) ve t i o! 1i (,r L i I i -~c r'rx r i no -nts IIiIL;' 'n inU m~:thud';, A pi -1,CM0119 fi'~)W 1~-LCU jllrtivlll~ (T.I.'S) -4- --,_i con~,I),"("Ll orl luvuls 01 nitr:i'-_:;, poiyjj~, ,vts, ard phytosterolL. Prof*:'i-u-ss %..,as j;:idc it) ivcveral areas of i;ctivity: 77 A nut., grotip of compounds, fatty alcohols, and esters, were ' developed for tobacco sucker ccntrol. 2) The source of N-210 and Pb-210 in leaf tobacco -was identified. Tbe.,,e elements can be reduced if necessary. 3, AfluWxins were eliminated as licssible sii.C)ke hazard. 4) ViZu variation in leaf tobacco of alkaloids, polyphertols, phytosterols and nitrates was found in Nicotiana plants. Because of limited funding situation and lit.,flited tobacco material, most of the 'leaf samples produced were DrTly used for.chemical analysis. Some of 6 ein were selected- later for ~shcjrt- tarot bioassay of leaf extract Ito &'.Vl-i"ic nz feret-_es were found among these samples. B. 1969-1973 Ye conducted well designed experimatifs of definite objectives for- identification-of p racu rso r- product relationsMp among leafi smoke, and various aspects. of biological responses-. At thp__sma tiviLi., eXVPriW4-"ts vmr;a conducted and progress was made on geneticsi clilture, curing, pos-t- - harvest tr(~atj-eiits, pesticides and physi6logical and biochemical studies of. LW 302058800 BATCo document for Province of British Columbia 19 April 1999 07 _~ '7 - z7z~ C 0 i. ~'J I AV, V" r, Lui .,I,u rr, (hnMr,f;, C-1 V piysica I prnp.-rti(,,_- of thc I ini.,Jn-d pi-oc:i,cf 3) Post-harvcsst troi---t and p:,.~: ui iwj 0-catment of Icaf tobacco such as freeze dryin,, and other processes way reducc the undesireble cumhu!~tion pk-oducts. 4) EstablWi the relationship beticen nitrosamine contpnt in the smoke and the nitrogenous fraction in leaf of different tobacco samples. 5) Thrutigh correlation studies, some precursor product relation7. ship was found among various leaf components, smoke compo-sition and biological activ4ty. 6) Bioassay uf verious pesticides including soil fumigants, nemati ci des and Suckering chemicals resulte"d-in. identification - of certain undesirable materi-als. _7 or 4 4caf t6bacx1b, the desirable characteristics are fire--holding capacity, K.- ceI I wall substances, ftitrate "itrogan aspartic acid anO malic acid.' The variables which show positive associatJon Witb- TPM, phenorls and BaP are trichome number, leaf thickness, moisture oquilibrium, aI. 0 -tal, alpha -total nitrogen, tQt taloids,to total free amino acids. dimethylamine, total polyphenkils, oxalic acid, 302058801 BATCo document for Province of British Columbia 19 April 1999 _X 3 ~_ _4 Zi 111-14 J~Y I I tti! ::LCL) ypi-~~, v r ~~o L it O-oqeii I ei,;, I i s 1,,c i- ri nn aq- 1-,A.!~ ionship Va am' prr P I' ou, 1 ii-iI1),J;J0II 901&r~Ud fi_~" W,'~ Q f i: tV th contri butcs to 1.1a, P of rc C 19 71 19 7 periods are exploratory it: na"itre, for the purpose cf The prpvious V L defining the role of agricultural research in sm"itiq and iicalth program. 1 -xt period, we hope that a "theoret-cal model" of a the activities of the riL safer tobacco leaf cart be established and woft to.-rd that rz3al 1) Develop reliable short-term bioassay systems for screeni rig large numbcrs of samples generated by plant scieiitists~ Fach system may meet a specific objective. 2) Establish a "Theoretical Model" or "llypotheti.cal M*del" for a safer tobacco leaf. This would inplude defining the botanical properties (such as trichopie nu!~ber, ,'leaf shape); physical chernical.pr6perties (such as alkaloids, phytQsterols, polyphenols. wax, terpenes , potassium); and agronGmic aspects (such as -3-1 e1 d , uniform maturity, curabil-ity, pesticides, fertilizers). 3) S~reen irom availablc Tobacco Introductions (T.I.) for various -dz:: &I e jeure-vical mo0el. 4) Produce, as allowable uncker practical conditions, pesticide- frce", tobaccos frow both Surley and fluc-cured types.and r,~akn 302058802 BATCo document for Province of British Columbia 19 April 1999 (A ew'.' ovj: till C- "tid If.6 vi IIt 11c, R-) V j Pc r h: lei) 111-1119 (111.r) I i o ronmn ,,,l 1of pr~,cursors c,, co1I1rj':j:f prol.1--i Oltl de';irahle and illiprovf I L 6) Condvc-t swoke end lrio,t~isay studies of tob~!LLQ varictics or breedli-ig line-, varying in wax content and terpone content. 7) Conduct precursur-product correlation study of leaf, smoke and biological activi-ty with Burley-tobacco types similar to that with flue-cured type. 8) Studies on nitrosamine. Conduct inhalation studies and establish the critical dosage level of riitrosamines. Examine the different effects between nitrogen application in the field and those spiked onto leaf tobacco, detemine the volatile and nen- volatile nitrosainines in the smoke. 9) Conduct comp)ete leaf, smoke and-bioas-say studies of a series T _vV. -of szq;1C5-W5d% di'll"ei-e-A 76 1 ic 'ii di i o ne e s in v ng 0.4,0.6s.-0.8. and, I.O..percent nicotine tobacco from. f I ue-cured and,flurley types. 10) Continue studies on-treatment of cured-leaf,. -This inc-ludes phys i-cal (e.g. freeze drying), chomical (e.g.. A00i tiv 5), and biological (e.g. ferwntation, bacteria)-means. 302058803 BATCo document for Province of British Columbia 19 April 1999 vot'.' o' Itit''!, wl (,I-, gill 11.1r, .~i Mud, ted-inin,,.!c-, for c~~11 CU1i--1)1- -, proi.(.;,. f-.'J hybi-li- zation 01)d Select ion. CIO--Q coorvilwl iml Uild NCI will, 1~c essentiijl in coridUCting the%e studics. Ccrt~-in studir-1 will lip under- taken through ccllabw~ation with scicntists of state . 1 pi-ivat(: insti-l'- T. C. Tso -13 July 24, 1~lf 302058804 BATCo document for Province of British Columbia 19 April 1999