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Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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protein is a DNA-dependent ATPase with DNA helicase activity . The role of this<br />

ATPase/helicase in the various RAD3 functions identified remains to be established .<br />

The RAD2 gene is DNA damage-inducible . Following exposure to a variety of DNAdamaging<br />

agents steady-state levels of RAD2 mRNA increase -3-6 fold . Induction is<br />

positively regulated . Cis-acting sequences required for induction have been<br />

identified by deletion mapping <strong>and</strong> mutants have been isolated that are defective in<br />

induction of RAD2 . The amino acid sequences of the RAD10 <strong>and</strong> RAD3 genes share<br />

homology with the human excision repair genes ERCC1 <strong>and</strong> ERCC2 respectively .<br />

Additionally, the RAD10 gene partially camplements the phenotype of mammalian cells<br />

defective in the ERCCI gene . Thus, genes for NER are apparently conserved in<br />

eukaryotes .<br />

177<br />

IN VIVO EVALUATION OF CYCLOACTIVE AND CLASTOGENIC EFFECTS OF BEET ROOT COLORS . N .C . Froes <strong>and</strong> N . V. Garcia,<br />

TEILC-'UNESP, Seo Jose do Rio Preto, S ;o Paulo, Brazil .<br />

The recent development of food industry has made food additives a relevant cause of human cancer,<br />

particularlydue to the autagenic activity of several synthetic food colors . The knowledge of mutagenic<br />

effect of natural food colors gives scientific support for the replacement of synthetic by natural ones .<br />

Two different forms of beet root colors were tested, the form I without nitrate residues <strong>and</strong> the form II1<br />

with nitrate residue . The coloring active principle of both extracts is the betanin pigment which gives the<br />

characteristic beet root purple color . llatagenic effects were tested in vivo . The experiments were carried<br />

out with bone marrow cells of males <strong>and</strong> females Rattus ~norvergi~cus var . star six-seven weeks old, 90-100g<br />

of weight, orally treated with both forms for one wee , w-3tTi- 0 .02 mg <strong>and</strong> 5 .0 mg of betanin per 100 g of body<br />

weight per day ; the bone marrow material was collected at the 8th day . For the bone marrow cell experiments<br />

two different control groups were established : a negative group of untreated animals <strong>and</strong> a positive group<br />

of animals treated with 5 .0 mg of cyclophosphamide per 100 g of body weight 24 hours before sacrifice .<br />

Mitotic index (MI), chromosome anomalies (CA) <strong>and</strong> micronuclei frequencies were recorded . Slides of bone<br />

marrow were analysed in blind tests . There were no differences in MI, micronuclei, <strong>and</strong> CA frequencies, when<br />

the treated samples were compared with the negative control . The positive control presented a gross MI<br />

reduction <strong>and</strong> an increased micronucleus <strong>and</strong> CA frequency. These results suggest that aiie both forms of the<br />

compounds were metabolized <strong>and</strong> inactivated in non-mutagenic derivates, justifying the absence of S vivo<br />

cycloactive <strong>and</strong> clastogenic effects . The present results seem to support that beet root color is a sa er<br />

alternative food additive . Economic <strong>and</strong> technical restraints were not considered .<br />

178<br />

PREDICTION OF POSSIBLE CARCINOGENS, TUMOR-PROMOTERS AND ANTI-TUMOR<br />

PROMOTERS IN THE GLANDULAR STOMACH . C . Furihata <strong>and</strong> T . Matsushima,<br />

Institute of Medical Science, University of Tok~o, Tokyo (Japan)<br />

An in vivo short-term assay method was developed for prediction of<br />

carcinogens, tumor-promoters <strong>and</strong> anti-tumor promoters in the gl<strong>and</strong>ular<br />

stomach . In this method, test chemicals are administered to male F344<br />

rats . Then tumor-initiating activity is assayed by measuring inductions<br />

of unscheduled DNA synthesis (UDS) <strong>and</strong> DNA str<strong>and</strong> scission (by alkaline<br />

elution method), <strong>and</strong> tumor-promoting activity is determined by measuring<br />

induction of ornithine decarboxylase (ODC) activity <strong>and</strong> stimulation of<br />

replicative DNA synthesis (RDS) in the gl<strong>and</strong>ular stomach mucosa. By<br />

this method five possible gl<strong>and</strong>ular stomach carcinogens, glyoxal,<br />

methylglyoxal, diacetyl, 3-diazo-N-nitrosobamethan <strong>and</strong> 1-nitrosoindole-<br />

3-acetonitrile were identified . Hickory smoke condensate, with or<br />

without treatment with nitrite, was found to be a possible gl<strong>and</strong>ular<br />

stomach carcinogen . In addition, 20 possible gl<strong>and</strong>ular stomach tumor<br />

promoters were identified, including various sodium salts, potassium<br />

salts, <strong>and</strong> an ammonium salt of food additives <strong>and</strong> bile acids . CaC12 was<br />

found to be a possible anti-tumor promoter in the gl<strong>and</strong>ular stomach : its<br />

administration inhibited stimulation of replicative DNA synthesis<br />

induced by subsequent administration of NaCl, a tumor promoter in the<br />

gl<strong>and</strong>ular stomach .<br />

179<br />

IN VIVO MUTAGENICITY TESTS ON POLYPLOID INDUCERS<br />

Furukawa,A ., Ohuchida,A . <strong>and</strong> Wierzba,K .*<br />

Drug Safety Research Lab . <strong>and</strong> * Biological Research Lab ., Taiho Pharmaceutical<br />

Co .,LTD . . Kawauchi,Tokushima 771-01 Japan .<br />

The micronucleus (MN) <strong>and</strong> a chromosomal aberration (CA) tests were used to<br />

study in vivo the mutagenicity of polyploid inducers in mouse bone marrow cells .<br />

Five chemicals, e .g . ethyl vanillin, narcotine, p-nitrotoluene,<br />

diethylstilbestrol, thiabendazole, were used as specific in vitro polyploid<br />

inducers (1) . These chemicals were suspended in olive oil <strong>and</strong> were injected<br />

intraperitoneally to BDF1 male mice (8 veek-old, 23 .2-28 .5g) . In pilot PQN-test,<br />

frequencies of micronucleated polychromatic erythrocyte (MNPCEs) varied from 0<br />

to 0 .4% depending on the dose <strong>and</strong> sampling time . The main test was carried out<br />

http://legacy.library.ucsf.edu/tid/clb93d00/pdf<br />

1989 EMS Abstracts 63<br />

Notes

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