Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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TUMORIGENESIS PROFILES IN THE NCI/NTP DATA BASE
R . Benigni
Istituto Superiore di Sanita'-Lab . Tossicologia Comparata ed Ecotossicologia
Rome - Italy
The tumor profiles of 139 chemicals,resulted to induce cancer in rodents in the NCI/NTP
experimentation, were analysed by multivariate statistical methods . The study pointed
to four main aggregations of the chemicals . Benzene had a profile non classifiable in
any of the four classes . From the point of view of risk assessment, two classes of car-
cinogens ( composed by only 7 and 9 chemicals with peculiar profiles ) were associated
with Ames test mutagenicity . No apparent association with Ames test result was observed
for the two other classes, that included the large majority of chemicals . Thus, the cl-
assification of carcinogens based on the whole spectrum of hystopathological evidences
did not parallel the repartition between Ames positive and Ames negative chemicals .
This suggests that the case for "primary" carcinogens ( genotoxic, and assumed to pose
a greater risk ), and "secondary" carcinogens ( presumably producing the carcinogenic
effects via non genotoxic mechanisms ) is rather speculative, and at present cannot be
taken as a basis for risk management .
48
MUTAGENICITY STUDIES ON SIX PESTICIDES IN lIICE .
D .K .Benova, I . Roupova, A . Yagova, A . Vuglenov, M . Bineva' . Institute of Nuclear Medicine,
Radiobiology and Radiation Hygiene, Sofia 1756, Bulgaria . *Cell . Biol . Lab ., Gen . Biol .
Dept ., University of Plovdiv, Plovdiv, Bulgaria .
Six pesticides widely used in agriculture were studied for their Sp vivo mutagenic
activities . They were : (a) insecticides - Vaztak (Pyrethroid), Dursban (Organophosphate) ;
(b) fungicide - Rubigan (Pyrimidine) ; and (c) herbicides - Cliphozat (N-Phosopho-methylglycine),
Stomp (Nitroaniline) and Diquat (Dipyridilium) . The production of polychromatic
erythrocytes with micronuclei at different times after oral administration of an 1/2 LD50
dose was examined . All pesticides except Gliphozat are mutagens with Rubigan the weakest .
Doses of 1/4 and 1/8 of the LDsa ware found to be ineffective .
The frequency of chromosome aberrations in mouse bone marrow cells after administration
of Stomp or Diquat in doses of 1/2 the LDyo were also examined . A tendency of increasing
numbers of hyperdiploid calls and acentric fragments was observed only with Stomp in the
late sampling hours (96 and 120h) .
The mutagenic effect of selected pestides is discussed . The data suggest that these
chemicals are (at least Stomp and Diquat) more aneugens than clastogens .
49
UNSCHEDULED DNA SYNTHESIS (UDS) AND DNA ADDUCTS IN HEPATOCYTES AND GERM CELLS OF
2-ACETYLAMINOFLUORENE (2AAF)-EXPOSED F-344 RATS . K .S . Bentley, G .T . Arce,
K . Randerath, P .K . Working, D .A . Agostinelli, T . Smith-Oliver, and B .E . Butterworth,
Haskell Laboratory, E .I . du Pont de Nemours 3 Co ., Newark, DE (USA), Baylor College of
Medicine, Houston . TX (USA), and CIIT, Research Triangle Park, NC (USA) .
In vivo/in vitro hepatocyte and spermatocyte UDS assays are used to quantitate
chemicalTyinduced DNA repair in liver and germ cells . The ability of these assays to
detect DNA damage was compared to quantities of DNA adducts . Male F-344 rats were
exposed by gavage to 0, 0 .5, 5, 50, or 250 mg/kg 2AAF . Twelve hours later, primary
hepatocyte and speSmatocyte cultures were prepared and the cells were incubated in
medium containing H-thymidine . UDS was measured by autoradiography as net nuclear
grains (NG) . DNA was isolat~ from the remaining cell suspensions and 2AAF-DNA
adducts were evaluated by the P-postlabeling method . A dose-related increase in NG
was observed in hepatocytes ; but a positive UDS response was not detected until a dose
of 5 mg/kg was reached . Both N-(deoxyguanosin-B yl)-2-aminofluorene (dG-C8-AF) and
N-(deoxyguan%sin-8-yl)~AAF (dG-C8-AAF) were detected at doses as low as 5 mg/kg
(approx . 10 and 10' adducts/nucl4otide, respectively) . Only dG-C8-AF could be
quantitated at 0 .5 mg/kg (approx . 10- adducts/nucleotide) . A correlation between DNA
adducts and the UDS response was observed . In spermatocytes, UDS was detected only at
250 mg/kg . Unlike the liver, only dG-C8-AF was detected in the germ cells . It was
present at doses as low as 5 mg/kg (