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.