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Titolo:
LYMPHOCYTE MUTANT FREQUENCY IN RELATION TO DNA ADDUCT FORMATION IN RATS TREATED WITH TUMORIGENIC DOSES OF THE MAMMARY-GLAND CARCINOGEN 7,12-DIMETHYLBENZ[A]ANTHRACENE
Autore:
MANJANATHA MG; LYNCOOK LE; CULP SJ; BELAND FA; HEFLICH RH; AIDOO A;
Indirizzi:
US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,HFT-120 JEFFERSON AR 72079 US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV BIOCHEM TOXICOL JEFFERSON AR 72079
Titolo Testata:
Mutation research
fascicolo: 1-2, volume: 357, anno: 1996,
pagine: 89 - 96
SICI:
0027-5107(1996)357:1-2<89:LMFIRT>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
ETHYL-N-NITROSOUREA; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; PERIPHERAL-BLOOD; FISCHER-344 RATS; FEMALE RAT; F344 RATS; INVIVO; INDUCTION; 7,12-DIMETHYLBENZ(A)ANTHRACENE; 1,6-DINITROPYRENE;
Keywords:
HPRT; 6-THIOGUANINE-RESISTANT; SPRAGUE-DAWLEY RAT; N-ETHYL-N-NITROSOUREA; P-32 POSTLABELING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
M.G. Manjanatha et al., "LYMPHOCYTE MUTANT FREQUENCY IN RELATION TO DNA ADDUCT FORMATION IN RATS TREATED WITH TUMORIGENIC DOSES OF THE MAMMARY-GLAND CARCINOGEN 7,12-DIMETHYLBENZ[A]ANTHRACENE", Mutation research, 357(1-2), 1996, pp. 89-96

Abstract

The ability of the rat lymphocyte hprt assay to detect tissue-specific carcinogens was evaluated using 7,12-dimethylbenz[a]anthracene (DMBA) administered under conditions that result in mammary gland tumors. Fifty-day-old female Sprague-Dawley rats were given single doses of 5 and 20 mg/kg DMBA by gavage, and the frequency of 6-thioguanine-resistant (TG(r)) T-lymphocytes was measured over a period of 21 weeks. A time- and dose-dependent increase in mutant frequency was found, with a maximum frequency found 9-15 weeks after treatment with 20 mg/kg of DMBA, Rats were also dosed with 1, 2.5, 5, 10, 15 and 20 mg/kg of DMSA and assayed for TG(r) mutant frequency 10 weeks after treatment. A significant linear dose-response was found, with all the DMBA doses resulting in significant increases in mutant frequency. To determine whether or not DMBA-induced mutants in rat lymphocytes reflected the DNA damage in the target tissue, rats were treated with 5 and 20 mg/kg of DMBA and spleen lymphocytes and mammary gland tissue were assayed for DNA adduct formation 1, 3 and 7 days later. A similar pattern of P-32-postlabeled adducts, involving both dG and dA nucleotides, was found in DNAfrom both the target tissue and the surrogate lymphocytes, Adduct formation was dose responsive in both tissues, with a 2.3- to 4-fold higher concentration in mammary gland as compared with lymphocytes, These results indicate that the rat lymphocyte hprt assay is sensitive to a mammary gland carcinogen and that similar types of DNA adducts are associated with both the lymphocyte mutants and the mammary gland tumors induced by DMBA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 15:38:04