Five of 12 forms of vaccinia virus-expressed human hepatic cytochrome P450 metabolically activate aflatoxin B sub 1

Journal Article · Fri Jun 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.12.4790· OSTI ID:6108419

Aoyama, Toshifumi; Yamano, Shigeru; Gelboin, H V; Gonzalez, F J ^[1]; Guzelian, P S ^[2]

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1. National Institutes of Health, Bethesda, MD (USA)
2. Medical College of Virginia, Richmond (USA)

Twelve forms of human hepatic cytochrome P450 were expressed in hepatoma cells by means of recombinant vaccinia viruses. The expressed P450s were analyzed for their abilities to activate the potent hepatocarcinogen aflatoxin B{sub 1} to metabolites having mutagenic or DNA-binding properties. Five forms, P450s IA2, IIA3, IIB7, IIIA3, and IIIA4, activated aflatoxin B{sub 1} to mutagenic metabolites as assessed by the production of His revertants of Salmonella typhimurium in the Ames test. The same P450s catalyzed conversion of aflatoxin B{sub 1} to DNA-bound derivatives as judged by an in situ assay in which the radiolabeled carcinogen was incubated with cells expressing the individual P450 forms. Seven other human P450s, IIC8, IIC9, IID6, IIE1, IIF1, and IIIA5, and IVB1, did not significantly activate aflatoxin B{sub 1} as measured by both the Ames test and the DNA-binding assay. Moreover, polyclonal anti-rat liver P450 antibodies that crossreact with individual human P450s IA2, IIA3, IIIA3, and IIIA4 each inhibited aflatoxin B{sub 1} activation catalyzed by human liver S-9 extracts. Inhibition ranged from as low as 10% with antibody against IIA3 to as high as 65% with antibody against IIIA3 and IIIA4. These results establish that metabolic activation of aflatoxin B{sub 1} in human liver involves the contribution of multiple forms of P450.

• OSTI ID: 6108419
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:12; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFLATOXINS
ANIMALS
ANTIGENS
BACTERIA
BODY
CLONING
CYTOCHROMES
DIGESTIVE SYSTEM
DISEASES
DNA
DNA HYBRIDIZATION
DNA-CLONING
ENZYME ACTIVITY
GENETIC ENGINEERING
GLANDS
HEPATOMAS
HYBRIDIZATION
HYDROGEN COMPOUNDS
IMMUNOLOGY
ISOTOPE APPLICATIONS
LIVER
MAMMALS
MAN
MATERIALS
METABOLIC ACTIVATION
MICROORGANISMS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PARASITES
PIGMENTS
PRIMATES
PROTEINS
RECOMBINANT DNA
SALMONELLA
SALMONELLA TYPHIMURIUM
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VACCINIA VIRUS
VERTEBRATES
VIRUSES