Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part II: Mechanism-based inhibition of rat liver microsome-mediated aflatoxin B1-DNA binding by the candidate antimutagen 7,8-diacetoxy-4-methylcoumarin

7,8-Diacetoxy-4-methylcoumarin (DAMC), with no prerequisite for oxidative biotransformation has been reported to produce suicide inactivation of microsomal cytochrome P-450-catalysed formation of aflatoxin B1-8,9-oxide that binds to DNA. Parenteral administration of DAMC to rats caused significant i...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1998-10, Vol.6 (10), p.1895
Main Authors: Raj, H G, Parmar, V S, Jain, S C, Goel, S, Singh, A, Gupta, K, Rohil, V, Tyagi, Y K, Jha, H N, Olsen, C E, Wengel, J
Format: Article
Language:English
Subjects:
7-Alkoxycoumarin O-Dealkylase - metabolism
Aflatoxin B1 - metabolism
Aflatoxin B1 - pharmacology
Animals
Antimutagenic Agents - pharmacology
Biotransformation
Bone Marrow Cells - drug effects
Coumarins - metabolism
Coumarins - pharmacology
Cytochrome P-450 CYP1A1 - metabolism
Dietary Supplements
DNA - drug effects
DNA - metabolism
Male
Micronucleus Tests
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
Mutagens - metabolism
Rats
Time Factors
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Summary:7,8-Diacetoxy-4-methylcoumarin (DAMC), with no prerequisite for oxidative biotransformation has been reported to produce suicide inactivation of microsomal cytochrome P-450-catalysed formation of aflatoxin B1-8,9-oxide that binds to DNA. Parenteral administration of DAMC to rats caused significant inhibition of AFB1 binding to hepatic DNA in vivo as well as AFB1-induced micronuclei formation in bone marrow cells. These results highlight the antimutagenic potential of DAMC.
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(98)00111-4