These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.
Pubmed for Handhelds
PUBMED FOR HANDHELDS
Search MEDLINE/PubMed
Title: Mutagenesis of certain activated carcinogens in vitro associated with genetically mediated increases in monooxygenase activity and cytochrome P 1-450. Author: Felton JS, Nebert DW. Journal: J Biol Chem; 1975 Sep 10; 250(17):6769-78. PubMed ID: 808546. Abstract: A bacterial mutagenesis assay and genetic differences in microsomal CO-binding cytochromes were combined in vitro to evaluate the metabolic activation of several known carcinogens to frameshift mutagens. With the use of liver fractions from C57BL/6N and DBA/2N control mice and mice treated in vivo with 3-methylcholanthrene, beta-naphthoglavone, phenobarbital, or 2,3,7,,-tetrachlorodibenzo-p-dioxin, the in vitro mutagenicity of 3-methylcholanthrene, 6-aminochrysene, and 2-acetylaminofluorene --but not benzo[a]pyrene==is closely associated with the genetically mediated difference in both aromatic hydrocarbon-inducible aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity and new cytochrome P1-450 formation; such an association between 7,12-dimethylbenz[a]anthracene or benz[a]anthracene activation to mutagens in vitro and these genetic differences between C57BL/6N and DBA/2N mouse strains in uncertain. The Salmonella typhimurium histidine mutant TA1538 is more effective than tester strains TA1537 and TA1535 in the determination of 3-methylcholanthrene mutagenesis in vitro. The relationships between the histidine revertant rate as a function of both liver protein concentration per plate and mutagen concentration per plate are illustrated for 3-methylcholanthrene, benzo[a]pyrene, 6-aminochrysene, and 2-acetylaminofluorene. With the use of offspring from the appropriate genetic crosses, the aromatic hydrocarbon-inducible hydroxylase activity appears to be expressed as an autosomal dominant trait, whereas the mutagenesis of 3-methylcholanthrene in vitro appears to be expressed additively; this apparent discrepancy probably reflects different proportional amounts of phenolic benzo[a]pyrene, compared with mutagenic 3-methylcholanthrene metabolites, formed by the monooxygenase(s). 3-Methylcholanthrene, 6-aminochrysene, and 2-acetylaminofluorene--but not benzo[a]pyrene--are each more mutagenic in vitro per molecule of cytochrome P1-450 than per molecule of CO-binding cytochrome other than P1450. Diethylmaleate, a compound which depletes flutathione content in liver, and 1,1,1-trichloropropene-2,3-epoxide, an inhibitor of epoxide hydrase (EC 4.2.1.63), were also studied in vitro. Diethylmaleate, and especially 1,1,1-trichloropropene-2,3-epoxide, increases the mutagenicity of benzo[a]pyrene, whereas no increases occur with 3-methylcholanthrene, 6-aminochrysene, or 2-acetylaminofluorene activation to mutagens in vitro. Both diethylmaleate and 1,1,1-trichloropropene-2,3-epoxide cause decreases in 2-acetylaminofluorene mutagenesis in vitro when liver fractions from phenobarbital-treated mice are used.[Abstract] [Full Text] [Related] [New Search]