Metabolism of fusarin C by rat liver microsomes. Role of esterase and cytochrome P-450 enzymes with respect to the mutagenicity of fusarin C in Salmonella typhimurium.
Fusarin C (FC) is a potent mutagen present on Fusarium moniliforme contaminated corn. This compound requires metabolic activation for which microsomes from phenobarbital-induced rats are most effective. Inhibition of the simultaneously induced esterase activity, which produced a less mutagenic metabolite, doubled the mutagenicity of FC. Carbon monoxide inhibited the mutagenicity of FC, suggesting the involvement of a heme containing enzyme. However, monoclonal antibodies specific for the phenobarbital-induced cytochrome P-450 enzymes PB-4 and PB-5, while inhibiting O-demethylation of p-nitroanisole and aflatoxin B1 mutagenicity, had not effect on FC mutagenicity. This implies that either these enzymes are not involved in the activation of FC or FC competes well with the antibodies for binding to the cytochrome P-450 enzymes. Two additional metabolites of FC were detected. One had an ultraviolet spectrum similar to FC: the other had a lambda max at 326 nm, and its retention time on reverse phase HPLC was very sensitive to changes in pH.
Lu
S J
SJ
Department of Chemical Etiology and Carcinogenesis, Chinese Academy of Medical Sciences, Beijing.
Li
M H
MH
Park
S S
SS
Gelboin
H V
HV
Jeffrey
A M
AM
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001711:Biotransformation; D002248:Carbon Monoxide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007531:Isoflurophate / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000494:pharmacology; D011090:Polyenes / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D000348:Aflatoxins; D000911:Antibodies, Monoclonal; D011090:Polyenes; D007531:Isoflurophate; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; C041403:fusarin C; D004950:Esterases; D010634:Phenobarbital