A SUMMARY OF ONGOING RESEARCII
1967
Universit-y Of Kentucky
Tobacco, and Health
Research -P:ro(jram
Lexin n, Kept'Li
0,
302058529
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TABLE OF CONTENTS
Introduction . . . . . . . . . . . . . . . . . . .
. . . . . . . . . 1-2
k
Plant Science
rir. Rogger Anderson. . ... . . . . . . . . . . .
. . . . . 3
Dr. Lowell Bush . . . . . . . . . . . . . . . . .
. . . . . . . 4-5
r
Dr. Amber Cheng . . . . . . . . . . . . . . . . .
. . . .
6
Dr. Daniel Layten Davis . . . . . . . . . . . . .
. . . . . . . . 7
Dr, Claus Grunwald . . . . . . . . . . . . . . . .
. . . . . . . . 8
Dr. Carol Keller. ... . . . . . . . . 9
Dr. Paul D. Legg . . . . . . . . . . . . . . . . .
... . . . ... . 10
Dr. S. J. Sheen . . . . . . . . . . . . . . . . .
. . . . . . . .
Dr~. -John Sims, Dr.'"Barry 816omfield, -.12
6-
Dr.'.Charles Yang, Dr. Malcolm'Siegral. 13-14
:.e.~'icai Sci'ence-
1'#_
4
MLI A, D_ r. ~Iohn V, )aenner-, Dr. Dona
lk'Rurdic)C, Dt, -Harold biztc~n 15-16
Dr. -~Ilis V., Brown -
Dr. John rr"rt
Dr Jobn 14. Fattersori, Dr. Valter,T. Smith.
Dr.',Al6xiv Zane
~21
medical Scielic"--
-22
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(Table of Cuntents continued)
vr. James W. Flesher . . . . . . . . . . . . . . .
. . . ... . . . 24
Dr. Loren J. Hum-,roy . . . . . . . . . . . . . .
. 25-26
F-
Dr. Frnes-1 Lalonde . . . . . . . . . . . . . . .
. . . . . . . . . 27
D.,:. E. Doaqlas Rees, Dr. Paul Mandelstam . . . .
. . . . . . . . . 28
Dr. Irene Roeckel .. . . . . . . . . . . . . . . .
. . . . . . . . 29
Dr. Katherine Sydnor . . . . ... . . . . . . . .
.. . . . . . . . . 30
302058531
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INTkODUCTION
The University of Kentucky
Tobacco and Health Research Program
The Ur..~.versity of Kentucky Tobacco and Health
Research Progra- i 5
cooperative with the U. S. Department of
Agriculture, Agricultural
Research Sezvice. The program was developed to
elucidate the interre-
lationsbip -Zetween tobacco and human health.
Three major research areas,
plant sciences, chemical, and medical-- ~jciences,
each coordinated- with
the other, make the program at Kentucky unique.
The plant sciences
research emphasis is focused upon the synthesis of
health-related con-
stituants amd biological methods for their
control- The cheia~al sciences
are emphasizing the interrelationship between leaf
constituents and
-smoke composition. The medical sciencem. are
developing techniques to.more
precisely iclenti.fy biological activity oftobacco
smoXe fractions as
they relate to human health.
Although the'major objective-at pre'sient, is
dire-qted toward those COM-
ni r on i's being .
Pounds It re~late to c;a;x5clnog6nid activityi do'
ide'ikti
-.given to other _S~is~pect'rompounds. report-ad,
au healthy ejated.
r The program,
Yftfs~vion- Is-'to *7ftan1UF`t1ir tde,~hkc
Y
a more usef-al ptoduct.
en'i~s pre upon
Plant Siziendez Coiiutipu seht-in the tob CF6
-a o; Jea:~ -T,77
Lol.yzi-Lb givie~ j~j-aiiw uo rne amo.Ke traction
_.identifiect
i's - rran
_J~ t..to elucidate'the pathwa of"A' tfie6fS
-a:rAthe factors,
Y;; Yn
that Inf-luelace those, pathways-., Among loaf
Jo-ogstituorits- report e4- a~s
302058532
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2
compo,--inds. Research is now under wdy on tho
metabolic path,,,,ays, genetic
cont-_!~O, minoral auticition, and the influonce
of field and storage
microorganisms on leaf composition.
Chemical "cicnce: The health-I-ralated compounds
in tobacco prroku
6 o not necessarily exist in fresh or cured
tobacco leaf, but may arise
as by-products of pyrolysis. Leaf constituents may
be transmitted intac
in the smoke or break into numerous chemical
fragments or recombinz to
Wield heal-th-related compounds. The chemical
sciences are undertaking
two majot-#fforta.. (1) The study of the
interrelationship of leaf con-
stituents to smoke composition and the fate of
smoke-fractions 'in the
hott-cell as measuedd by analysis and (2) the
influence of pyrolysis
environment upon health-related compondhts in.the
smoke,
medical 9cie-tidest- -Compounds in...,Eobacco
smoke are identified as
biologically active (~ieaklth:-relatad) when tbeii
presence in the cell of"
!~th.lp jhqat diatur);>s the normal function- -of
that cell. once identified as
echni~ves to measure its import"Ce to
V.
Numan health 'must -be -developed.~. Present
teglMicLues f4or th6 bioassAy qf-
tobacco smo" 'constituents- leave much to be
-dpasired,. Medical sciefit~ltts
are researching- Aumr6vA I*vi" *ystei~i both-
intact and cultured, to
-the. re olvin4. er Of- the 41384
'POW ~y SYStQM.
302058533
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3
Dr. Roger Andcrson, Asst. Prof. (Adjunct) of
Agronomy
Spacialty: biochemical rebudrch
Interest-
Studying phenolic compounds in tobacco.
Specific objectives:
1. To develop methods for rapid and accurate
determinations of
microquantities of the principal polyphenols in
tobacco.
Methods receiving particular attention are
spectrophotometric
measurement and gas chromatography.
2.. To employ ang_~_ytical techniq,4es to
determine effects of
tobaccogenotype, growth, curing environment and
the compo-
gition of plant potlyphenols. Previous studies
indicate that
curing conditions greatly affect the concentration
of
pbenols.-In. the leaf.
Goals:.,-
-To -reduce or-eliminate
p~enols,*knowncarcinoge'As,-from thd
'm 86~k -xwthod -at.. Rzodu'ding-a-safer
o
302058534
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4
Dr. Lowell Bush, Asst. Prof. of Agronomy
Specialty: -plant physiology (seed physiology)
Interest:
Study the biosynthetic and metabolic pathways cf
secondciry
amines and other nitrogen compounds, ubz;erving
their translo-
cation and redistribution in tobacco plants.
Specific objectives:
1. To study ho w enzymes influencu ti-te
assimilation of nitrogen
in tobacco.
2. To study the movement and accumulation of
nitrogen com-
pounds, particularly secondary am:Lne alkaloids.
ThIs is
done-by treating tobacco plants with various
chemicals
which retard water loss by the plant but.not plant
growth.
Leaves, stems androots are then separated, and the
various
alkaloids'in iaadh plant -part' are determ;Lned
and acorrelated
with the amount of wai,-er whidb has move.d
through the plant
-parts.
3. To investi amounts of onzymic,act ivity necess
ary f
-gate the or
-synthesis of compchinds ult .imaItIi;lY-
amine. alkalclida! --within the
plant..,.Enzypicabbivities arb
measured in tobacco plants at,various stages 0
deve op-
-irom. ental
ment ~ and in ttosa7 produced under diftex4anv
env.
conditions,
xA7
302058535
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5
plants. The concentration of nitrosamines,
kr.,-',-iI c:arc-.-,OCjCIISI
in tobacco smoke may be depondent on levels of
nitrate and
secondary amines in the tobacco leaf.
0
302058536
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Dr. An,,-'er Chonc;, Asst. Prof. (AdjuncL) of
Agronoi-,iy
Specialty; lipid metabolisms
interest:
investigate sterols and residual compounds in
tobacco related
to the use of sucker control cheirticalS and other
treatmentc.
spccific Onjectives:
1. To slitVCy how Lhe sterol content of tobacco is
aftected by
pre- and post-harvest envixonmental conditions.
2. To study the enzymes involved in the formation
and trans-
formation of sterols during growth and curing..
3. To 'study the effects of suckering chemicals on
the chemical
composition of-field-grown tobacco. Focus
Is.placed-on-the-
amount of sucker control residue present in green
and
6,
cured tobacco leaf, activity of the chemicals, and
thdir
effects on-plant constituents.
Goals:
1. To regulate-the metabolic pat
cionteni in tobacco., sterols-pay be._-
2. -To determine if res idues from supker control
chemicals'arii
302058537
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Dr. Daniel Layten Davis, Asst. Prof. of Agronomy
Specialty: physiological genetics
Inter-estt
To study the genetic control of synthetic pathways
involvinq
sterols and certain nitrogenous constit"ents in
to'bacco.
apecific objectives:
1. To analyze varied tobacco tissue samples to
determine
genetic control of sterols and nitrogenous
constituents.
Special emphasis is placed on the secondary amines
such a s
anabasina, diethylamine, myosamine, nornicotine,
piperidine---
and the related compounds nitrosamine and
diazoalkanes.
2- To produce seed -of aeveral generationt. from
tobacoa_,srai~letieq
which are low and high in the stat ed compounds.
3. To meabilrd the effect of environmental
and-idevelopmental
factoia gn'these c unds~
OMPO
4. Attwpj_l to develop pure lines which po"ess
very.low and
ittem
Goals i
."To ftudy- the '9enetId'6on'tr;oI of.
hea1th-x4blatiA c6nstit;uents in
tobaccd. This goal.will'be att~6pted by invqst
igtt ifig, -the
'hesis,' --well *&-mo"
fac -in- biocl)er~ical -synt as
of inharlitance,. of these 'compouride.
302058538
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Dr. CI-aus Grunwald, A--.-,t. Prof. of Agronomy
Specialty: steroid metabolism, plant growth
regulators, ion uptake
interest;
i*nvPf4ViUmt,& the rrctabAJ--; piucesses and
possible regulation of,
sterols and indoles in plants.
Specified Objectivos:
1. To develop a method which wi.11 yield
quantitative and
qualitative analysis of sterols. The analytical
method
will be based on liquid/liquid and gas
chromatography in
conjunction with ultraviolet and infrared
spectroscopy.
2. To isolate and identify sterols found in fresh
and cured
tobacco. To follow sterols synthesis at different
physio-
logical ages of.the tobacco plant.
nes by measuring-
3.. To-study the effect of steeols on call membra
the diffusion of radioactive compouiids~through
the membrane.
Also 0-hanger. in membrane structure Ifill
.1m,.,irivestigated.,
Goa I,S -
To ascertain if tobacco Osqr-910- -are, bLe" th_r~
la'te4.
f~om.tobacco-may ii4giuenao o~~ 1.,d4vizion -,jand
cell permeability
il~~ much the pame. way as.-certain oteroidhormqne
.-,'If*.~ite~rols
have a, physiological, gunction in i6biacco, the
lowbst functional
t4 air, aaav_it~ -may --alob
sterol level. must Ip determiRod A~4.qe
affect tfil~. whole, zi4abolic bioi~rnther-is- of
tha plant.
302058539
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A';
Ye
Dr. Carol Keller, Asst. Prof. of Agronony
Specialty: plant pY,..siology and bicchemistry
Interest:
To inve6tigate the biosynthesis and metabolism of
rutin and
certain sterols.
specific Objectives:
1. To study the olienolic c6ni.LiLuents of fresh
tobacco
leaves and determine how environmental factors
modify
these physiological processes. Emphasis is on the
study of chlorogenic acid and rutin, the principal
poly-
ph-anola of tobacco..
2. To isolate and characterize enzymes necessary
for the
synthesis of p1henols in"tobacco.
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Dr. Paul D. :,I~tgg, Asst. Prof. (Adjunct)
Of_A9I:UI-IUI-WY
Spociaity: quLr~titative genetics and biomctrics
Intere-St:
1. The s-_-,idy of characters in tobacco that are
inherited
in a ;uantitative manner..
7, Ouantitative genetics tbeory,
Specific objectives:
1, To o7->tain information on the inheritance of
ag=nomic
and chemical characteristics in tobacco.'
2. r2o.utilize genetic information to develop
effective
breeding methods for Improving burley tobacco
vari~_-Ues..
Goals:
1. To determine. the poteAtialities- and
limitatto" of
imprbving tobacco -through cp.netics.
12. 'To outline and utilize the-beat
piocedu;es-fo; developing
burley varieties most ~assful to' tobacco
-groweri; and.
302058541
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Dr. S. J. Shuun, Asst. Pro-k. of Agronomy
Spccialty: physiological genetics
1"LU.A. U~- L :
Investigate the generic control of cheaMical
con5tituents in
tobacco in order to incorporate
desirable-charactori5tics into
commercial tobacco varieties.
Srecific ObjcctivcG~
1. To study gene enzyme systems in relation to the
metabollism
of secondary metabolites in tobacco.
2. To survey the spectrum of enzymes involved in
the regulation
of the synthesis of pdlyphdnols and
secondary--amines.
3. To study substrate specificity, activation and
suppression
of enzymes correlated with the quality and
quantity of
second.-iry metabolites.
4. -,To dis-cover regulator_y-mochanismsof
gena-action during
the varl us Olases -L6f tobac-~, development,
% -4-
To-peoduc4i'tobar-co, vakri
"dties witl~ reduced qu&ntitie~-,-of c6hdary
Thislit- -96~06d&&yj -tas are-p're-
petaboli
curs6rs 9f suspe ct:4d heailth-!~-xe,lated
cqnstituints'in tobacco.
j3 moke.
302058542
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!7-
M,
12
Dr. John Sima, Asst. Prof. of -Aqr0:10mN'
-3 arry Dloom
Dr. field, Asst. Prof. of Aqronomy
Specialty: nitroqen trans fox-mation in
ill nitr,,4ta, nutrition of plants
Interest:
investigate how varying 5oil, fertilizer, cultural
practices.
varieties, and curing methods affect the levels
niF
which are conSidered to bc pi:ecursors of
nitrosamines in
LoIjacco smoke.
Specific objectives:
1. To alter the composition of tobacco by changing
soil type,
nitrogen fertility, soil moisture and other
cultural con-
ditions.
2. To idefttify specific factors in the growth
environment
that effect the aitrogen nutrition of tobacco
and-to re-
late these factors to tbe,syntheeis of nitrogen
compounds-
Goals:
To develop the agronomic- practices necessary.
for__pri~dictinq
and controlling the r_ttZZ;g!v1oUs compounds
of -tobacco plants. Cqpposition of th.e~ tobacco
leaf is affect6d'.
greatly by the fertility levels'of the soil, i~
whiCh tobacco
Factors affecting the n n composit~on.of toba=o'
is grown..
are particularly importair~t inany attempt- ammit
C-
jc~ Oata~aL- t
Of, --Zdt ~A ines.
302058543
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13.
Dr. Charles Yang, Asst. Prof. of Plant
Pa%';-iology
Specialty: fungal physiolog-Y, soil ricrobiol-igy
and electron
microscopy
Di% 1,,lalcolm Sic4el, Asst. Prof. oi Plant
Pathnlocvv
Specialty: fungal physiology
Interest:
Investigate the--carcinogenic and other toxic
metabolites pro-
duced by tobacco fungal flora.
Specific objectives:
I.- To study changes of the yearly occurrence,
distribution
and composition of fungal flora from dark
air-cured and
burley tobacco.
2. To estimate the frequency of occurrence and
toxin produc-
tion in.yearly_changes- of the Aspqrgillus
flavus--oryzae
group, fungi.of the-dematicae.
1. To test thei'fungal ext racts--for toxiz~s
using bacteria, 'chick
embryo or animal t.issue culture as a bioassay
method.
4,,... To study the physical,and chemical
characteristics Qf fungal
toxins. Included are the effects of envir6nmetUt
P~1, tem-
~"nutiienti ~Lfid of, z~gal cultures on, toxin Z
r
produption; Al Q hold toxifis affect
respiration,,'
_growth,
metabolism and 1~7rpeabllit
_y 6f,. organism6,
1. To idgntify-the fungi-In' tobacco heaves whicb
produce to.ic,
-metabolite* and Which . ories -,.;'kre
cibnoistent in .to'baeco~
--- - -- ---- ---
302058544
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Proccssin.. pl:elir,;
14
Prqscr", "'ary f'ndilqs
known the
carci
lsOli"ted
f--;- r'OV'111 Pr,,d,,,6
2- To ly funqi
Production. unmental Conditions
that
3- IOX.In
establish activities of tc"iz
Order to d0terMin, colnUntirl'.
sIgnifica,ce as
ii-~ cOMPOUnds.
health-related
302058545
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7 71
N.X,
Dr. joh)-i F. licnn,r, A:~i_-it. Prof. of
Agr,wiomy
Dr. Donald 3urdick, A6st. Prof. (Adjunct) of
Agronomy
Dr. Harold R. Burton, Asst. Prof. of Agrzanomy
Specialty: organic analysis, Lobacco and
Interest:
To develop and evaluate C-igarattc modifici:s
which alter smoke
composition.
SpCciC_ic Ob*ecLives:
1. To investigate the offectb of various
"Cheruical modifiers"
on the burn characteristics of tobacco and the
composition
of its smoke. Several classes of chemicals are
being in-
Ve9tilatdd which imclude: oxidizing and reducing
agents,
flame-proofing compounda, hydrated salts, free
radical
initiators and scavengers, and other chemicals
knowxL-to
alter-tbe.combustibility of cellulose and lignin.
Burn
o_O temperatu Iies of the treated zigarettes,
as,well,zs .the
levels of total paXticulate matter, nicotine,
pheno.1,
benzo(a) pyrens, and-othex-smoke constituents are
being
determined.
2--; To inveftijftit t- he rnode of the 1 deg
dation of.tbese 1
rma ra
_iNv
c
'hemically treated tobaccos by thermougravirrtric
analysis
ands d'iffer=tial tberma'l anilyses.
._1*41_._t1,__w1&i11cn, red=e~ the concentration
of
those constituenta in-tobacqo si~oke. which have
baen imp~i_
Fated,ih the__bealj:h problem.: Upon-achieving a
significant
302058546
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aitQraLlor. in the 1,_!vels ct one or more of
thc,(-_- col-,-
AV-
stituents, 6moke
the condensate will be z;ubmitL.d for bic-
assay.
oals!
Nil-
To study in depth the chemical composition of
cigarctte smoke
to include the mechanisms of formation-and ive --
selec rcdu~z
tion of various smoke -constituents which ar e
health-related.
L
T.
00
4-
302058547
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Dr. E),Jis V. Brc)wii, Prof. ana' of Department of
Clioizii-f;try
Specialty: organic ChEl.-MiStry-rLaCtiOn
mechanisms, hcterDcyclic
chemistry, carcinogcnesis
Interest:
To invastigate the chemical composition of the
heterocyclic
Ova bases in cigarette smoke.
Specific objectives:
To-isolate and identify nny nitrozdutines tound in
tobacco and
tobacco smoke.
Goals.
~74
To determine if secondary amines intobacco and
tobacco smoke
may react with thd nitrogen oxides-fotmed during
combustion to
produce nitrosamines, known carcinogens.
-4-
302058548
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lu
Dr. JDhn Green, Assoc. Prot. Of Agronomy
5 experimental analytical biochemistry,
instrumentation
5,pecialty: I
development, and sub-cellular physiology
Interest:
1. To analyze tobacco and tobacco smoke
condensates.
2. To conduct research and development of
experimental tech-
niques on -instrumentation re].Rt--,~d t-t-
tobaccc and hcalth
research.
3. To manufacture experimental cigarettes and
prepare cigarette
smoke condensate.
4. To conduct research and testing of conventional
and ex-
perimental bioassay procedures.
5. To conduct research on the subcellular fate
of-tobacco
.smoke constituents.
Specific-objectives:
1. To dire t an analytical activities laboratory
for service-_
tQ, tobacco -and health researchers a~; the
University of
Kentucky. Det.em. inatiQfis of-
cohstitizehts'conITUOnly -used
for xneasuring t0aqqo,charAc.~;eristics,
-aLud.-qua1it~y wiM be_..
2,, 'To dirffct a - Smoke c6ndensratq
--p6itegtopp-ill,
vices inclucte the-,ma-hufacture
of'-akperimeritAl' cigarettRas,
selection and'stor e, of.
standardiZVd'_&i9,Uiat;~si chino
ag
ttouAtw Mmi,
and.,smoke condensato std~ringi
3.. To desipt in,--the d.evdlQpment. qf
-experimental,- ~procedures,
Ch
302058549
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4. To con6uct StUUiOS Of--Lhe subcullular fate ol
smoke constituents.
Goals:
1. To develop and evaluate now analytical
proced-ures for
de-termining health related organic compounds in
tobacco
and tobacco smoke and for determining their effect
on cells
and tissues. The procedures will be directed
toward de-
termining environmental or genetic effects on
large nuziibers
of experimental samples. A quick estimation of
chemical
changes in tobacco will therefore be availablea
2. To-define biological tolerance of tobacco smoke
and its
constituents in-its entirety.
302058550
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Dr. J01,11, M. PattCr3011, .-rOf- Of C.-,0mi`;trY
Specialty: organic clhemistr7--chemistry of
heterocyclic ~Ompounds,
A
nitro czmpoundg, high temperature rcactions and
photc--
chemical reactions
,7 ~_4 - jW
Dr- wp~ltci: T. Smith, Jr. , Prof. of chemistry
,
Specialty: organic chemistry--relation of
structure to biological
activity, organic synthesis and bigh temperature
reactions.
Interestz
investigate the chemical composition of the
pyrolytic products
of amino-acids.
Specific objectives:
To determine whether and how certain-vatiables
(such as :9truc-_
tural alterations and temperature) influence
pyrolysate
composition and whether low temperAtute
alterations of amino
acids (amines. and substituted diketopiperazines)
are inter-
diates in the high temperature.process.
e
m
Goals.
To provide.informarion about the,nature of the
pXocess by which
argamic moleculizA. are. Arenes and
substances which may be cazclnogonic, 'I is
-believed-
that -an-understanAiiig Qf the. basi6 pyrolyzi&
proce" 'will fa'
cilitate the-eventual ra461ution, of,
thei"tobacb6-health, -ptoblem.
*The compounos atuaied 'here occur..,,iz the
Irot-i~iU-
-zx -ia67U_ia.sujpply cionsiderable infoimatlpn
about'
th e%eneration qf'carclin a ic mgterial durizig
the burnin
n
302058551
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Alexis _-'anc-, Asst. Rrof. of Ajronomy
r:t~~
ty: plant polyphcnulics, isolatiuii and
idcntificrt:ion
Interest:
To dcvelop an improved anAlyt-ica_' tor
cietormining
polyriuciear aromatic hydrocarbons and
heterocyclic compounds
in cigarette smoke.
Specific objectives:
To develop isolation techniques and more rcliaLl=
analytical
methods for determining the concentration of
certain poly-
nuclear hydrocarbons in cigarette smoke. The
method requiring
the shortest performance time using the smallest
number of
cigarettes and with repradutibility comparable to
present.
methods will be preferred. Chromatographic,
ultraviolet and
.,.,sRectrophotofluotometric techhiques are used.
Goals-
Todetermine the substances which account for the
carcino-
genicity in.tobacco smoke or-wbich,
acting-coordinately with'!
others, are inorf* carcinoge4# than".
as'-indiviftil cohipouncls,
-yj----6bMC,bT- L-he-se'- ompoupd!i are
polynuclear Ako'
_Q~xita_Lpozaiba
mat ic:~byiil~c-~,rbons,
8552
30205
BATCo document for Province of British Columbia 19
April 1999


ir-
Dr !~orLcrt nraunL;t c _n, Tuj~_(,c. Pro 1. 0VaLho
I Qqy
Suorinl-,,: hi~~.DchcmjL;Lry of liver
Dr. Tatsuo Yznayama, Asst. Prof. of Pathology
Specialt.,; lung disoasc. haamat-1 jy
Interest:
Lnvestiqate the biological as6aying of various
tobaccos, smoke
oT.ensates, and related substances for
carcinogenic, cocarcino-
c
ge.-Iac. and related activities,
Specific objectives:
I- To evaluate research samples of known
carcinogens and smoke
condensates for their tumorigenic effect on mice
by the
nouse-back painting techniqu6.
2. To determine.tumorigenic effect of..samples of
tobacco ex-
tracts and cigarette smoke condensates,' including
samples
controlled by Aifferent agronomic, cultural,
curing, genetic,-
andling and marketing conditigns. -Tobacco leaf
extracts
are,also-tested- Smoke. condensates'
from'cigarettes, pon-
7
taining various chemical modifiers aLteting smoke
comp6slt.lbil
Goa
To dej;.Vrmine the degreel9f carcinogenicity.or
cocarcinocjenickty
Qf tobacco samples.
302058553
BATCo document for Province of British Columbia 19
April 1999


2.3
Dr. Grace Doniiellj,, InsLr,,cLor of Cell
13ic)lc)gy
7
R! SPLcialtY: mitotic phenomena, cell division
phenoinena
InteresL:
iiivestigate tracheal rings as a bioassay
technkque.
Specific Objectives:
To grow in vitro cultures of tracheal epitheliiLr,
under
con-
trollod t.;ii:euntstances, to expose them to
tobacco smoke conden-
sate and to test them for possible effects.
Goals:
To determine the effect,of tobacco on tracheal
i
r
ngs grown in
tissue cultlite-for us in developing a new
, rapid bioassay
system.
302058554
BATCo document for Province of British Columbia 19
April 1999


'111., 4-7-r-,
Dr. James W. Flesher, A--L;t. Prof. of
Pharmacology
SpQcialty: biochemistry, pharmacology
Interest:
1,ive.-stigate the distribution and metabolism of
benzoia)pyrene.
Specific Object ve.5:
1. To determine the effects on rat
tissue--marinary, Lung
r benzo
and (a)pyrene, 3-methyleholanthxene and
=mom
7,12-dimethylb~anxanthracane.
V~r
27-7
2. To determine the effect phenanthrene has on
benzo(a)pyrane.
M,
3. To identify metabolites in tissue as a result
of the
a W-, -UP
prosence 6f -phonanthrene and benzo(a)pyrene.
Goals:
To determine -chemica.1 changgpL--in.
benzo(a)pyrene when is in
tissue, and the-effect of benzo(a)pyrene-and its
p3Zq on
ducts..
tiss ue..
40471
302058555
BATCo document for Province of British Columbia 19
April 11999


Dr. Loren J. HuT~..-.rrey, As~,,i)c. Prof. of
Surgary and Celi ijiology
Specialty: _--,miunology of carcinogenesis
Interest:
Investigate the response of virus-cell culture
systems to
tobaccc, smoke condensates.
Specific Ob3ectives:
1,,, ~tiieiy -tb~- a(-tion of methylebolanthrei-io
-with anc. without
a cell-free extract of a
methyleholanthrene-induced sar-
coma in-vivo and in vitro as a carcinogen or
co-carcinogen.
2. To determine if the cells maintained-in tissue
culture and
exposed to..methyldholanthrene contain a
virus-like agent
and/or to develop the neo-antigen seen with
transformed
malignant cells in-vitro.
3. To determine if the sera from rabbits injected
with the
methy1cholanthiene-induc6d"sarcoma or mice. immune
to, the
methyleholanthrene sarcoma conta-in -a- tupiot
specillic antigen.
4. To pre'pare a cell-free, extract from
cigarettip smo.le con-
der-S 4te- Inoue esarcmas apa inocu;La r-n s no,
'and in-mc -E~O 'determini the car-
Mp t i ue cu_1tiire9_._-
cinogenic or- co-carcinoejenic pctency of such
an-extract,~
lmwanolp%ic atiAdies will.be performed. to
determine whethor
ea_ a& a.. i4~v_
transfqrmed cell$,.
Goalas
DOM& rar-, W_
302058556
BATCo document for Province of British Columbia 19
April 1999


cigarette smoke condensates in order t-:
dcvclc-,,-- ~ now
bioassay system.
2. To determine the role of condensates in t1jo
format-, oil
u.Z normal cells and relationship of the
colidensaZes to
factors contributed by the host during the
maliqzant pro-
cess.
Iz-
302058557
BATCo document for Province of British Columbia 19
April 1999


71
Z..'
Ve..,
L K-~
I)r. Ernast Lalonde, A2st. Prof- of oral Pathology
Specialty: oral patbology, oral absorption
Interust:
Investigate the effect of tobacco smoke condensate
on oral
carcinogenesis in hamsters.
Specific ObjcctivE..,:
To measure the amount of abwrrtior and
tuia-Lgeaicity ot radio-
active carcinogenic, cocarcinogenic substances or
cigarette
smoke condensate on the cheek pouch of Syrian
hamsters.
Goals:
Ta -develop a new bioassay metbod for deter*ininq
tr-e carcin0_
genicity or cocarcinogenicity of cigarette smoke
condensate.
302058558
BATCo document for Province of British Columbia 19
April 1999


"t*~
X9 'I
A. Iq
5421i, ~V2 I
A-
T_
28
Dr. E. Douglaz Rees, A:isoc. Prof. of Medicine
Dr. Pa-..~! Mandelstam, Assoc. Prof. of Medicine
S ecialty: bi-~t-~-mi Rtry,
!I-'trarest:
investigate absorption ot carcinugenx and
Structurally related
non-carcinogens from the gastrointestinal tract of
rodents.
specific objectives:
To conduct in vivo (by intragastric adzhini st
ration) and in
vitro (using small.inteatinal sacs) studies on the
absorption
and the tissue-concentration of the carcinogens
7,12-dimethyl-
benz(a)anthracene, 3-methylcholanthrene
anclbeazo(a)pyrene and
the non-carjaizkogens Shrysene,
benzo(ghi)fluoranthene, and benzo-
(e)pyrene in the gastrointestinal and other
tissues of rats.
302058559
BATCO document for Province of British Columbia 19
April 1999


so
c loeckel, At~,SOc- prof, of Pathology
Iren ..
Speclalty, pzthology
investigate respiratory epithelial cell turnover.
Spe-c-ific
o discover during their life span Wbat is the
normal ccil
21,
in the "inbred high spontaneous tumor" strain
"M
mice (A/Lj) and the--low incidence tumor- strain
mice (C57 BL/6j)
at various ages.
Goals:
To eOtzibliSh respiratory epithelial cell turnover
as a test
system for determining carcinogenicity
and.cocarcinogenicity
of cigarette smoke constituents,
302058560
BATCo document for Province of British Columbia 19
April 1999


3 0
Dr. Natlierine Sydnor, Assoc. Prof. cf Medicine
Specialty: cndocrinclogy, biochemistry
Interest:
Investigate the effect of aqueous extracts of
cigarette smoke
condensate on the formation of tumors in rats.
Specific Objectives:
1. To administer tobacco smoke condensate in the
drinking water
of rats, noting its effects--toxicity, Pff,-cts on
weight,
amount of water consumed.
2. To determine the effect of-an aqueous extract
of cigarette
smoke cofiddilgate on the induction of cancer,
Benzo(a)pyrene
is administered, animals with tumors sacrificed,
and patho-
loclital tissues prepared for- microscopic
examination.
3. To determine the effect.of the aqueous
extraq~_.pn liver
enzyme activities.involved in the metabolism of-
poLlynuclear
aromatic hydrocarbons.
Goals:
I--- To eva.Lua e.Lii
the inductiori of cancer.:by -different, tyve-. of
dotage.
'To evaiuate- tfie'- 'carcinogenic 'effect
afaqueous extracts-, of
of tu3dara at~ ndi~ff t__'
3. To re,~om"nd the pqssible.'applicatioh of
these-resuits
__k6ward ~!1.0 Y~t Qf et now b
7-= v_A
302058561
BATCO document for Province of British Columbia 19
April 1999


Dr. Daniel WeisK, PrDl:- Of Pat"01097Y
Specialty: pathology
Interest:
-W
machanism5. of carcinvgenesiS in wholc animals;
roles of vircil
and chemical agents independently and in
combination in tne
induction of pulmonary tumors; variability of
strain and
individual susceptibility.
Specific objectives:
,-AX^W- X r 1. To obtain selected skin specimens
ftum wice whob.
were reVlarlq, painted with tobacco &moke
condensate.
Then tha cells are examined under the electron
microscope
for.structural changes.
To investigate-Ly transplanting ihduded ttufiorss
those tna~--
lignant characteristics which can be identified
early in
tumor development.
To investigate the inter-relationship of
genetically stable
animal strains, nononcoge.nic'virmAos, and
chemical ca~rcino-_
gens in the development of pulmonary tumors.
Goa Is i
-4,
1. To determine'the,,t=origenic effect of
different types 0
~2' To recommend the possible' al~pUcation of
thsse~~results
toward th~pF deVOopuwizit~ ol a iiew.bioaasay
system.--.
Y.Tlil'-, -7--i
302058562
BATCo document for Province of British Columbia 19
April 1999


J)r. r-"ji'Ll - I Assoc. Prof. It Bi0che"stly
V~h -~ t C
Ilectron transport, phospl,,,~ lipid netabolis-.-a
nterest:
stigate the electron transport Syster, 0t
bacLe.L.L11-
inve . us and StaPhYlOcOccrs d1irens-
nelaninoqenic
Sp,cific objectives: y pigments Of __~;r-e
To-iCOIN". apd, chara.cterizO respiratOr
multiple enzyme electror, trallsport system of
BacteriO616
melaninogenicus. By adding hemin to the growth
medium the
. formed, Then respiratory
electron transport sYstem 's
ptc)teins are_ identified and assayed I I~,Y
pigments and _flaLvd
'known Methc(is
-factor.1 iry,lv,d in the formation If
investigatd thiff
2. To
em in tactetiodeg melaninoqenicuS
tbe electron tranapor~t sYBt
are rel4ted t-0 neoplastiC f0-m-ati0l".
and how they
-n.tfie electron
the effdat -of the carcinOgen NO .ONO
3. To studY
*.k -*he -effect -Qf
"k0 deVZ109. arl El
4.
enicus, that effQqt,-whidh
lAigiieking
iodes me'J'anin0a
-19 wil_1 then be
plastic cel ..Vhis System~
in no".
ion (a
-ihe bilitY Of the thiocYana,_
Ut_i I iz d tci teirt -a
Jactron trant;po~i-
a"e
04
System-
W
'Goals -
cf the
r#.e 'th6 fo=ation.
t;~rs WhIch
Va
302058563
BATCo document for Province of British Columbia 19
April 1999


electron transport system in Bacteriodes
a 'ase for the development of a bioassay method
f-,r deter:.ining
the carcinogenicity and cocarcinogenicity of
tobacco smoke.
302058564
BATCo document for Province of British Columbia 19
April 1999