Environmental and Molecular Mutagenesis - Legacy Tobacco ...

401 1989 EMS Abstracts 139
CARCINOGEN INHIBITION OF HAMSTER BUCCAL POUCH EPITHELIAL CELL Notes
REPLICATION jj`[ VITRO M . Nagabhushan, P. Polverini and D . Solt . Northwestern
University Department of Pathology, 303 E . Chicago Ave ., Chicago, Il 60611
Precancerous lesions induced in rodent liver with chemical carcinogens are
resistant to the inhibitory effect which these agents exert on liver cell replication .
This functional property of "resistance to cytotoxicity" has been used to detect
very early precancerous liver cell populations . We wish to apply this same strategy
to detect and characterize precancerous epithelial cell populations in hamster
buccal pouch(HBP) -- a tissue which is structurally and functionally similar to human
oral mucosa . As a first step toward this goal we have developed an approach
to monitor HBP epithelial replication, and its inhibition, upon exposure to carcinogens
L vitro . In a representative experiment, fragments of HBP were incubated
in supplemented media for 24 hrs in the presence and absence of 7,12-dimethylbenzanthracene(DMBA)
or methylbenzylnitrosamine(MBN). [3H]Tdr was added to
the media for the final 2 hrs of incubation and acid insoluble counts were determined
. At concentrations of 0 .15, 0.30, and 0 .60 mM, DMBA and MBN inhibited
[3H]Tdr incorporation by 35%, 76%, 87% and 91%, 93%, and 98% respectively . We
conclude that this approach, combined with autoradiography, may be useful for
in vi detection of precancerous HBP lesions resistant to chemical carcinogens .
402
INHIBITORS OF NITROSATION IN VITRO . M . Nagabhushan,
Northwestern University, Department of Pathology, 303 E . Chicago Ave.,
Chicago, IL 60611 .
Nitroso-compounds are mutagenic/carcinogenic compounds formed by the
interaction (nitrosation) of amine/arnide and nitrites . Human stomach maintains acid pH, is
the most probable site of formation of nitroso-compounds . Fish, preserved meat,
vegetables and drinking water are rich sources of amines/amides and nitrites . Several
inhibitors of nitrosadon are known to be present in human diet . In the present study some
of the inhibitors of nitrosation of tnethylur ea and fish extract by sodium nitrite at pH 3 .6
and 2.0 are reported. Salmonella strain TAIOO and TA1535 are used to monitor the
formation of mutagenic nitroso-compounds . The extracts (principles) of turmeric
(curcumins), betel leaf (eugenol, hydroxychavicol), tea (Tannic acid) and catechu (catechin)
exhibit dose dependent inhibition of nitrosation . The simultaneous treatment of inhibitor
with precursors is essential for the inhibition . Pre or post-treatment of inhibitor does not
modify the mutagenicity of nitroso - compounds. In case of phenolics pm - hydroxy
group is essential for nitrosation inhibition . The nitrosation inhibition by phenolics in
through the scavenging of nitrite ions from the media, thus making it non-available for
nitrosation.
403
TRENDS IN ENVIRONtWNTAL CARCINOGENESIS
B. Nagarajan, Cancer Institute, Madras - 600 020 INDIA
rlost cancer is caused or promoted by life style and environmental
factors . Carcinogenesis is a multiple process involving initiation, promotion
and progression . Identification of several risk factors helps
evolve effective approaches to control and contain the disease . In our
laboratory, we carried out in-depth studies on hexachlorocyclohexane
(ttCH), a commonly used pesticide . It is a hepatotoxic compound with
potential tumorigenecity that induced gamma glutamyl transpeptidase
positive foci, mostly in periportal hepatocytes . A complete carcinogen
such as dimethylaminoazobenzene hits selected target cells and only that
clone's cells proliferate to malignancy . In HCH treated cells, marker
analysis both for differentiation and proliferation established an
epigenetic promoter component .
Clofibrate is an extensively used hypolipidemic drug . Cytogenic
studies on drug-treated rat bone marrow cells and human lymphocytes in
vitro showed minimal damage that repaired to normal on withdrawal of the
drug . Biochemical studies also agreed with this observation . However,
if the cells were pre-exposed to an initiator such as diethylnitrosamine
and followed with clofibrate, they tend to exhibit tumorigenecity . A
similar hazard risk assessment is warranted in the use of halogenated
hydrocarbons .
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