Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B sup 1 metabolism in human liver

Journal Article · Thu Nov 01 00:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.21.8306· OSTI ID:5820706

Forrester, L M; Wolf, C R ^[1]; Neal, G E; Judah, D J ^[2]

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1. Imperial Cancer Research Fund, Edinburgh (England)
2. Medical Research Council Labs., Carshalton (England)

Liver cancer is a major cause of premature death in many areas of Africa and Asia and its incidence is strongly correlated with exposure to aflatoxin B{sub 1} (AFB{sub 1}). Because AFB{sub 1} requires metabolic activation to achieve a biological response, there is a need for detailed knowledge of the mechanism of activation to assess individual risk. The authors carried out an extensive study using a total of 19 human liver samples to determine the individual variability in the metabolism of the toxin to mutagenic or detoxification products and to identify the specific cytochrome P-450 forms involved in these processes. Metabolism to the toxic 8,9-epoxide or to products mutagenic in the Ames test was found to exhibit very large individual variation. These data demonstrate that, although P450IIIA probably plays an important role in AFB{sub 1} activation, several other cytochrome P-450 forms have the capacity to activate the toxin. Similar considerations apply to detoxifying metabolism to aflatoxin Q{sub 1} and aflatoxin M{sub 1}. The levels of expression of many of the forms of cytochrome P-450 involved in AFB{sub 1} metabolism are known to be highly sensitive to environmental factors. This indicates that such factors will be an important determinant in individual susceptibility to the tumorigenic action of AFB{sub 1}.

• OSTI ID: 5820706
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:21; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
AFLATOXINS
METABOLISM
CYTOCHROMES
BIOCHEMISTRY
MICROSOMES
AUTORADIOGRAPHY
AFRICA
ASIA
IODINE 125
LIVER
MAN
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BODY
CELL CONSTITUENTS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HAZARDOUS MATERIALS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
MAMMALS
MATERIALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
PRIMATES
PROTEINS
RADIOISOTOPES
RIBOSOMES
TOXIC MATERIALS
TOXINS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics