Effect of (+)-catechin, dimethyl sulfoxide and ethanol on the microsome-mediated metabolism of two hepatocarcinogens, N-nitrosodimethylamine and aflatoxin B1.
Effects of catechin, a plant phenolic flavonoid, and of the commonly used organic solvents dimethyl sulfoxide (DMSO) and ethanol (EtOH) on the microsome-mediated metabolism of two hepatocarcinogens, N-nitrosodimethylamine (NDMA) and aflatoxin B1 (AFB1), are presented. Using hamster liver microsomes as a source of mixed-function oxidases, it was shown that catechin at 0.1-0.2 mM levels had no effect on the oxidation of either carcinogen. However, at 1-5 mM levels it caused a concentration-dependent inhibition (38-70%) of the formation of formaldehyde from NDMA, and at the 5 mM level it caused a 40% inhibition of AFB1-DNA binding. DMSO and EtOH totally inhibited NDMA demethylase activity but had little effect on the binding of AFB1 to DNA. These observations indicate that the mixed-function oxidases (cytochrome P450) essential for the metabolic activation of these carcinogens exhibit different sensitivities to different inhibitors.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000139:chemically induced; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism
D000348:Aflatoxins; D000431:Ethanol; D002392:Catechin; D004247:DNA; D016604:Aflatoxin B1; D004128:Dimethylnitrosamine; D004121:Dimethyl Sulfoxide