The metabolism of aflatoxin B1 by hepatocytes isolated from rats following the in vivo administration of some xenobiotics
Isolated rat hepatocytes, an intact cellular system capable of performing phase I and phase II metabolism, have been used to investigate metabolism of aflatoxin B1. These cells were found to metabolise (/sup 14/C)aflatoxin B1 to aflatoxins M1 and Q1, and to radiolabelled polar material, presumably conjugates, as analysed by h.p.l.c., t.l.c. and radioactive determination. In vivo administration of the mixed function oxidase inducers, phenobarbitone and 3-methylcholanthrene, resulted in enhanced hepatocyte phase I (microsomal) metabolism of aflatoxin B1. In contrast to metabolism of AFB1 by in vitro subcellular systems increased production of polar material (conjugated metabolites) derived from (/sup 14/C)aflatoxin B1 was also detected in hepatocytes isolated from these pretreated animals. Formation of aflatoxin Q1 by isolated hepatocytes appeared to be mediated by cytochrome P450-linked enzymes whereas cytochrome P448-linked enzymes were apparently involved in aflatoxin M1 production. Chronic feeding of aflatoxin B1 to rats enhanced hepatocyte production of conjugated material only and did not elevate cellular cytochrome P450 levels, thus suggesting that aflatoxin B1 is not an inducer of its own primary metabolism.
- Research Organization:
- Toxicology Unit, MRC Laboratories, Carshalton, Surrey, UK
- OSTI ID:
- 5745389
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 4:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFLATOXIN
METABOLISM
MIXED-FUNCTION OXIDASES
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CARCINOGENESIS
CELL CULTURES
CHOLANTHRENE
IN VIVO
LIQUID COLUMN CHROMATOGRAPHY
LIVER CELLS
METABOLITES
MICROSOMES
PHENOBARBITAL
RATS
TRACER TECHNIQUES
XENOBIOTICS
ANESTHETICS
ANIMAL CELLS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
CONDENSED AROMATICS
DRUGS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
OXYGENASES
PATHOGENESIS
PYRIMIDINES
RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)