ACTIVATION OF TINIDAZOLE, AN ANTIPROTOZOAL DRUG TO A MUTAGEN BY MAMMALIAN LIVER S9

Tinidazole was found to display much higher mutagenic activity compare d to metronidazole in Salmonella strain TA100 and YG1029. Under anaero biosis, the specific activity of this nitroimidazole was enhanced, at least, by about 1.75-fold in TA100 and several fold in TA100NR relativ e to aerobic conditions. The mutagenicity in the latter strain with S9 mix became further increased by 2.5-fold under anaerobiosis, indicati ng the role of oxygen sensitive bacterial and mammalian S9 nitroreduct ases in the activation of the drug. The mutagenicity of the drug was s lightly lowered in TA100/1,8-DNP6 (O-acetyltransferase deficient), YG1 029 (O-acetyltransferase overexpressing) and TA100 in the presence of pentachlorophenol (PCP), an O-acetyltransferase inhibitor. These resul ts rule out the possible involvement of N-acetoxyarylamine pathway in the metabolic activation of these nitroimidazoles.