Environmental and Molecular Mutagenesis - Legacy Tobacco ...

407 1989 EMS Abstracts 141
GENOTOXICITIES OF N-NITROSAMINES ON DROSOPHILA AND A SEARCH FOR THE INHIBITORS OF THE Notes
TOXICITIES
Tomoe Negishi, Teruko Shiotani and Hikoya Hayatsu
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700, Japan
N-Nitrosamines are potent carcinogens for rodents, and their possible rr_levance to
human cancer has been intensively studied . In spite of the strong carcinogenic activities,
this class of compounds show only weak mutagenicity in the Ames bacterial tests .
We have now found strong genotoxicities for several N-nitroso compounds using the Drosophila
wing spot test . The test detects the activity of a given compound to cause gene
mutations and recombinations in the larval somatic cells . N-Methyl-N-nitrosourea (MNU)
and N-nitrosodimethylamine (NDMA) gave strong responses in this system, corresponding
to their potent carcinogenicities . Although N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
is a strong mutagen against bacteria, its genotoxicity on Drosophila was moderate . The
order of genotoxicities of these compounds in Drosophila was as follows ; MNU> NDMA 3-Nnitrosomorpholine
> N-nitrosopiperidine Z N-nitrosodiethylamine > MNNG > N-nitrosopyrrolidine
. Non-carcinogenic N-nitrosodiphenylamine and N-nitrosoproline were not genotoxic
to Drosophila . Since this Drosophila system seems to be suitable for the detection of
N-nitrosamine-mediated genotoxicities, it may be expected that this system is useful
to search for modulators of the genotoxicity . We examined the inhibitory potential of
several vitamins on the NDMA-mediated genotoxicity in Drosophila . We observed, however,
no suppressive effect in 6-carotene, vitamin B1, vitamin C or vitamin D2 on the genotoxicity
of NDMA .
408
EFFECT OF POLYUNSATURATED FATTY ACID ON DMH INDUCED COLON CANCER .
Nehru, B ., Kaur, R ., and Bansal, M .P .
Deptt . of Biophysics, Panjab University, Chandigarh-160014, India .
The :e is a strong positive correlation between the dietary fat consurption and the
prevalence of cancer of breast, colon, prostate and pancreas . The underlined mechanism
are quite complex, multifactorial and different in different types of cancer . The
present study was undertaken to study the role of unsaturated fatty acid in the initiation
of colon cancer by a chemical carcinogen 1,2 Dimethyl-hydrazine administered
in a dose of 20 mg/ g body weight / week subcutaneously . Three levels of dietary fat
manipulation was used 10% fat, 20% fat, and 30% of the total calore . Marked alteration
were seen in the drug metabolizing enzyme of colon follgwing a high fat dietary regime .
The observations were similar when DMH was given along with the high fat diet . The
cytochrone P 450 content showed a 4 fold increase in the high fat group . A decrease
in phase II enzyme namely glutathione and glutathione-S-transferase was noted .
409
A MULTI-FACTOR RANKING SCHEME FOR COMPARING THE CARCINOGENIC ACTIVITY OF CHEMICALS .
S . Nesnow, Carcinogenesis and Metabolism Branch, U .S . Environmental Protection Agency,
Research Triangle Park, NC 27711 USA
This activity scheme uses as its base, dose potency measured as TD50 (Gold et al .,
Environ . Health Perspect ., 67, 161-200, 1986) The TD,r0 is converted into an inverse
log scale, a decile scale, and then adjusted by weighting factors that describe other
parameters of carcinogenic activity . These factors include positive or negative
weightings for the induction of tumors at tissues or organs associated with high
historical control tumor incidences ; the induction of tumors at multiple sites ; the
induction of tumors in both sexes of the species ; and the induction of tumors in more
than one species . In order to construct a measure to express the inactivity of
chemicals as inducers of cancer, a measure analogous to the TD50 has been developed :
the highest average daily dose or HADD . The HADD is the highest average daily dose in
mg chemical/kg body weight administered in a chronic cancer study, and that did not
induce a statistically significant increase in tumors . HADD values were converted to
log decile units and adjusted by weighting factors relating to inactivity in both
sexes of a species, and the inactivity in more than one species . Three activity
ranking schemes were developed using a 142-chemical data set from NTP studies : the
Carcinogen Activity-F344 Rat, an activity scheme based on cancer data obtained with
the F344 rat ; the Carcinogen Activity-B6C3F1 Mouse, an activity scheme based on cancer
data obtained with the B6C3F1 mouse, and the Carcinogen Activity-Combined, an activity
scheme based on selecting data from both the F344 rat and the B6C3F1 mouse .
This is an abstract of a propos .d pnfantation and does not nflact EPA policy .
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