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

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 th...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1990-11, Vol.87:21
Main Authors: Forrester, L.M., Wolf, C.R., Neal, G.E., Judah, D.J.
Format: Article
Language:English
Subjects:
550601 - Medicine- Unsealed Radionuclides in Diagnostics
AFLATOXINS
AFRICA
ANIMALS
ANTIGENS
ASIA
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
CELL CONSTITUENTS
CHEMISTRY
CYTOCHROMES
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HAZARDOUS MATERIALS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
LIVER
MAMMALS
MAN
MATERIALS
METABOLISM
MICROSOMES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOLOGY AND NUCLEAR MEDICINE
RIBOSOMES
TOXIC MATERIALS
TOXINS
VERTEBRATES
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Summary: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}.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.87.21.8306