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Titolo:
GENOTOXICITY AND CARCINOGENICITY IN RATS AND MICE OF DIHYDRO-3-METHYL-7H-IMIDAZOLO[4,5-F]QUINOLIN-7-ONE - AN INTESTINAL BACTERIAL METABOLITE OF 2-AMINO-3-METHYL-3H-IMIDAZO[4,5-F]QUINOLINE
Autore:
WEISBURGER JH; RIVENSON A; REINHARDT J; ALIAGA C; BRALEY J; DOLAN LM; WILLIAMS GM; ZANG E; KINGSTON DGI; BASHIR M; SHU YZ; WILKINS TD; VANTASSELL RL;
Indirizzi:
AMER HLTH FDN,1 DANA RD VALHALLA NY 10595 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM BLACKSBURG VA 24061 VIRGINIA POLYTECH INST & STATE UNIV,DEPT ANAEROB MICROBIOL BLACKSBURGVA 24061
Titolo Testata:
Journal of the National Cancer Institute
fascicolo: 1, volume: 86, anno: 1994,
pagine: 25 - 30
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-REPAIR TEST; IQ; 2-AMINO-3-METHYLIMIDAZO)4,5-F>QUINOLINE; MUTAGENICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
J.H. Weisburger et al., "GENOTOXICITY AND CARCINOGENICITY IN RATS AND MICE OF DIHYDRO-3-METHYL-7H-IMIDAZOLO[4,5-F]QUINOLIN-7-ONE - AN INTESTINAL BACTERIAL METABOLITE OF 2-AMINO-3-METHYL-3H-IMIDAZO[4,5-F]QUINOLINE", Journal of the National Cancer Institute, 86(1), 1994, pp. 25-30

Abstract

Background: Compounds formed on the surface of fried or grilled meat and fish may be associated with increased risk of colon cancer. Normalintestinal bacteria can convert one of these compounds, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), to the 7-hydroxy metabolite, dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7-one (7-OHIQ), a direct-acting mutagen. Purpose: We studied the genotoxicity and carcinogenicity of 7-OHIQ to determine if it is responsible for the colon-specific activity of IQ. Methods: The effects of pure, synthetic 7-OHIQ on DNA wereevaluated in the Ames Salmonella typhimurium TA98 test, with and without an induced rat liver S9 fraction, and in the Williams DNA repair test using freshly explanted rat hepatocytes. 7-OHIQ was also subjectedto an in vivo bioassay for 21 months by long-term intrarectal infusion in male F344 rats, using IQ and N-nitrosomethylurea (NMU) given intrarectally as positive tumor-producing controls. The standard NIH-07 rodent diet was supplemented with 15% corn oil to maximize any effect ofthe infused materials on the colon. A parallel bioassay involved intraperitoneal injection of 7-OHIQ in newborn mice, followed by dietary administration from week 11 to week 67. Again, IQ and NMU were used as positive controls. Results: We confirmed that 7-OHIQ is a direct-acting mutagen in the Ames test, with added S9 liver fraction giving highermutagenicity. 7-OHIQ was negative in the Williams test, whereas IQ was positive. 7-OHIQ did not induce colon cancer in rats, and in the newborn mouse test it produced only a low incidence of liver neoplasms. Conclusions: 7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams tests; moreover, it is not carcinogenic, in marked contrast to IQ and NMU.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:31:54