In vitro prostaglandin H synthase- and monooxygenase-mediated binding of aflatoxin B1 to DNA in guinea-pig tissue microsomes

In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissues which have relatively low cytochrome P450 monooxygenase (P450) activity, we have examined prostaglandin H synthase (PHS)-mediated AFB1 activation ([3H]AFB1 —DNA binding). [3H]AFB1 was activated by bot...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1990-11, Vol.11 (11), p.1915-1919
Main Authors: Liu, Ling, Daniels, Jonathan M., Stewart, Richard K., Massey, Thomas E.
Format: Article
Language:English
Subjects:
Aflatoxin B1
Aflatoxins - metabolism
Animals
Cytochrome P-450 Enzyme System - metabolism
DNA - metabolism
Guinea Pigs
Kidney - metabolism
Lung - metabolism
Microsomes - metabolism
Microsomes, Liver - metabolism
Oxygenases - metabolism
Prostaglandin-Endoperoxide Synthases - metabolism
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Summary:In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissues which have relatively low cytochrome P450 monooxygenase (P450) activity, we have examined prostaglandin H synthase (PHS)-mediated AFB1 activation ([3H]AFB1 —DNA binding). [3H]AFB1 was activated by both purified PHS and microsomal PHS from guinea-pig kidney and liver, as well as by P450 in lung, kidney and liver microsomes, though P450-mediated [3H]AFB1—DNA binding in lung and liver was much higher than that catalyzed by PHS. Arachidonic acid (AA)-dependent [3H]AFB1 —DNA binding could be inhibited by the PHS inhibitor indomethacin (0.1 mM), but was enhanced by the P450 inhibitor SKF-525A (3 mM), confirming that the reaction was independent of P450. Pulmonary PHS-mediated [3H]AFB1 —DNA binding was
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/11.11.1915