EFFECTS OF ISOTHIOCYANATES ON CYTOCHROME-P-450 1A1 AND 1A2 ACTIVITY AND ON THE MUTAGENICITY OF HETEROCYCLIC AMINES

In this study we investigated the effects of phenyl isothiocyanate (PI TC), benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) an d phenylpropyl isothiocyanate (PPITC) on the mutagenicity of five hete rocyclic amines, IQ, MelQx, Trp-P-2, Glu-P-2 and PhIP in Salmonella ty phimurium strain TA 98 in the presence of liver microsomes from male S yrian golden hamsters. In addition, the effects of these isothiocyanat es on cytochrome P-450 1A1 and cytochrome P-450 1A2 activities were de termined by measuring the deethylation and the demethylation of ethoxy resorufin (EROD) and methoxyresorufin (MROD) respectively. With the ex ception of Trp-P-2, all four isothiocyanates significantly inhibited H CA-induced mutagenesis in TA 98 at concentrations of 0.05 and 0.1 mu m oles/plate. BITC was the only isothiocyanate tested that showed a dose -dependent inhibition of Trp-P-2-induced mutagenesis. These four isoth iocyanates showed a dose-dependent inhibition of EROD activity and, wi th the exception of BITC, of MROD activity also. This indicates that t he inhibition of HCA-induced mutagenesis correlates with the inhibitio n of cytochrome P-450 1A1 and 1A2. These P450s are known to metabolica lly activate HCAs. The inhibitory effects of the isothiocyanates were greater toward HCA-induced mutagenesis in TA 98 than toward EROD and M ROD activity. This indicates that the antimutagenic effects of PITC, B ITC, PEITC and PPITC on HCA-induced mutagenesis in Salmonella typhimur ium TA 98 involves more than the inhibition of cytochrome P-450 1A1 an d 1A2 activity in hamster liver microsomes.