Differential sensitivity of Ah-responsive mice to beta-naphthoflavone-induced metabolism and mutagenesis of benzo[a]pyrene and aflatoxin B1. 1985

V Raina, and P Koser, and H L Gurtoo

Effects of the administration to C57BL/6ha (Ah-responsive) mice of a low (10 mg/kg) and a high dose (150 mg/kg) of beta-naphthoflavone (BNF) on the hepatic microsome-mediated mutagenesis and metabolism of benzo[a]pyrene (BP) and aflatoxin B1 (AFB1) were studied. Hepatic microsome-mediated mutagenesis of benzo[a]pyrene was not enhanced by the low dose (10 mg/kg) but at the high dose (150 mg/kg) the mutagenic activation was enhanced several fold relative to control (corn oil-treated). Mutagenic activity of aflatoxin B1 was however depressed by both the low and the high doses of beta NF. These results are consistent with the effects of beta NF administration on hepatic microsome-mediated metabolism of BP to its phenolic products and on the metabolism of aflatoxin B1 to aflatoxin M1 catalyzed by aflatoxin B1-4-hydroxylase. Relative to control, pretreatment of the mice with 10 mg/kg beta NF did not induce aryl hydrocarbon hydroxylase activity (a measure of BP metabolism), however, the same pretreatment induced the metabolism of AFB1 to AFM1 by 2.7 to 4.7-fold. Microsomal preparations from 150 mg/kg beta NF-pretreated mice showed a 3-fold induction of aryl hydrocarbon hydroxylase activity and a 6.8-fold induction of AFB1-4-hydroxylase activity. These results suggest that two different enzyme systems are involved in the metabolism of BP and the metabolism of AFB1 to AFM1.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D005419 Flavonoids A group of phenyl benzopyrans named for having structures like FLAVONES. 2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D000348 Aflatoxins Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2. Aflatoxin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D001571 Benzoflavones Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered. Benzoflavone Compounds,Compounds, Benzoflavone
D016604 Aflatoxin B1 A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1. Aflatoxin B(1),Aflatoxin B,Aflatoxin B1 Dihydrochloride, (6aR-cis)-Isomer,Aflatoxin B1, (6aR-cis)-Isomer, 14C-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 2H-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 3H-Labeled,Aflatoxin B1, cis(+,-)-Isomer,HSDB-3453,NSC-529592,HSDB 3453,HSDB3453,NSC 529592,NSC529592

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