Genetic differences in metabolism of polycyclic aromatic carcinogens and aromatic amines by mouse liver microsomes. Detection by DNA binding of metabolites and by mutagenicity in histidine-dependent Salmonella typhimurium in vitro

Journal Article · Sat Mar 31 23:00:00 EST 1979 · J. Natl. Cancer Inst.; (United States)

OSTI ID:5973015

Levitt, R C; Pelkonen, O; Okey, A B; Nebert, D W

The metabolism of various carcinogens and other chemicals by genetically regulated increases in cytochrome P/sub 1/-450 content was studied with the use of liver from 3-methylcholanthrene (MCA)-treated C57BL/6N and DBA/2N mice. (P/sub 1/-450 is defined as that form(s) of cytochrome that increases during polycyclic aromatic inducer treatment of the laboratory animal or cells in culture. Two forms of P/sub 1/-450 have been characterized electrophoretically and catalytically, and even more than two are believed to exist.) Genetic differences were seen in the DNA binding of metabolites in vitro for: dibenz(a,h)anthracene, benz(a)anthracene, benzo(a)pyrene (BP), MCA, 7,12-dimethylbenz(a)anthracene, 2-acetylaminofluorene, and dopamine (approximately in descending order). Any difference for dibenz(a,c)anthracene or benzidine was very small. Marked genetic differences were observed in the mutagenicity (with Salmonella typhimurium tester strains TA1538, TA98, or TA100) in vitro for: 6-aminochrysene, dibenz(a,h)anthracene, dibenz(a,c)anthracene, ..beta..-naphthylamine, MCA, 2-acetylaminofluorene, BP, benz(a)anthracene, and ..cap alpha..-naphthylamine (approximately in descending order); the difference for 7,12-dimethylbenz(a)anthracene was very small. Important discrepancies for certain carcinogens therefore existed between genetic differences in metabolites binding to DNA and genetic differences in the metabolites causing mutation in this bacterial in vitro assay. These data may be useful for future studies with any of these chemicals in the extrapolation of genetic differences observed in vitro to differences in the risk of cancer associated with the Ah locus in the intact animal. Such genetic data for MCA and BP tumorigenesis have already been helpful in understanding the mechanism of chemical carcinogenesis.

• Research Organization: National Inst. of Child Health and Human Development, Bethesda, MD
• OSTI ID: 5973015
• Journal Information: J. Natl. Cancer Inst.; (United States), Journal Name: J. Natl. Cancer Inst.; (United States) Vol. 62:4; ISSN JNCIA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
AROMATICS
BACTERIA
BENZANTHRACENE
BIOASSAY
BIOLOGICAL EFFECTS
BIOLOGICAL VARIABILITY
BODY
CARCINOGENS
CELL CONSTITUENTS
CHROMOSOMES
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DNA
DOPAMINE
DRUGS
GENETIC VARIABILITY
GLANDS
HYDROCARBONS
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
LIVER
MAMMALS
METABOLISM
MICE
MICROORGANISMS
MICROSOMES
MUTAGENESIS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PHENOLS
POLYCYCLIC AROMATIC HYDROCARBONS
POLYPHENOLS
RODENTS
SALMONELLA
SALMONELLA TYPHIMURIUM
SYMPATHOMIMETICS
VERTEBRATES