title: Effects of isothiocyanates on cytochrome P-450 1A1 and 1A2 activity and on the mutagenicity of heterocyclic amines.
abstract: In this study we investigated the effects of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and phenylpropyl isothiocyanate (PPITC) on the mutagenicity of five heterocyclic amines, IQ, MeiQx, Trp-P-2, Glu-P-2 and PhIP in Salmonella typhimurium strain TA 98 in the presence of liver microsomes from male Syrian golden hamsters. In addition, the effects of these isothiocyanates on cytochrome P-450 1A1 and cytochrome P-450 1A2 activities were determined by measuring the deethylation and the demethylation of ethoxyresorufin (EROD) and methoxyresorufin (MROD) respectively. With the exception of Trp-P-2, all four isothiocyanates significantly inhibited HCA-induced mutagenesis in TA 98 at concentrations of 0.05 and 0.1 mumoles/plate. BITC was the only isothiocyanate tested that showed a dose-dependent inhibition of Trp-P-2-induced mutagenesis. These four isothiocyanates showed a dose-dependent inhibition of EROD activity and, with the exception, of BITC, of MROD activity also. This indicates that the inhibition of HCA-induced mutagenesis correlates with the inhibition of cytochrome P-450 1A1 and 1A2. These P450s are known to metabolically activate HCAs. The inhibitory effects of the isothiocyanates were greater toward HCA-induced mutagenesis in TA 98 than toward EROD and MROD activity. This indicates that the antimutagenic effects of PITC, BITC, PEITC and PPITC on HCA-induced mutagenesis in Salmonella typhimurium TA 98 involves more than the inhibition of cytochrome P-450 1A1 and 1A2 activity in hamster liver microsomes.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, CA 92350, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hamilton
authors.forename: R W
authors.initials: RW
authors.lastname: Teel
mesh_terms: D000818:Animals; D002243:Carbolines / Q000633:toxicity; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects*; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects*; D007093:Imidazoles / Q000633:toxicity; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity; D011810:Quinoxalines / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects; D013861:Thiocyanates / Q000494:pharmacology
chemical_list: D002243:Carbolines; D007093:Imidazoles; D017879:Isothiocyanates; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; D013861:Thiocyanates; C005441:phenylisothiocyanate; C093849:3-phenylpropyl isothiocyanate; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C058305:phenethyl isothiocyanate; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C031403:benzyl isothiocyanate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023847:Glu-P-2