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

Bioorg Med Chem. 1998 Oct;6(10):1895-904. doi: 10.1016/s0968-0896(98)00111-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • DNA / drug effects
  • DNA / metabolism*
  • Dietary Supplements
  • Male
  • Micronucleus Tests
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / metabolism
  • Mutagens / metabolism
  • Rats
  • Time Factors

Substances

  • 7,8-diacetoxy-4-methylcoumarin
  • 7,8-dihydroxy-4-methylcoumarin
  • Antimutagenic Agents
  • Coumarins
  • Mutagens
  • DNA
  • Aflatoxin B1
  • 7-Alkoxycoumarin O-Dealkylase
  • Cytochrome P-450 CYP1A1