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 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.
Raj
H G
HG
Department of Biochemistry, V. P. Chest Institute, University of Delhi, India.
Parmar
V S
VS
Jain
S C
SC
Goel
S
S
Singh
A
A
Gupta
K
K
Rohil
V
V
Tyagi
Y K
YK
Jha
H N
HN
Olsen
C E
CE
Wengel
J
J
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D016604:Aflatoxin B1 / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D001854:Bone Marrow Cells / Q000187:drug effects; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D019587:Dietary Supplements; D008297:Male; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism; D051381:Rats; D013997:Time Factors
C114369:7,8-diacetoxy-4-methylcoumarin; C114368:7,8-dihydroxy-4-methylcoumarin; D016587:Antimutagenic Agents; D003374:Coumarins; D009153:Mutagens; D004247:DNA; D016604:Aflatoxin B1; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1