Rl. Gupta et al., ACTIVATION OF TINIDAZOLE, AN ANTIPROTOZOAL DRUG TO A MUTAGEN BY MAMMALIAN LIVER S9, Mutation research. Genetic toxicology testing, 370(3-4), 1996, pp. 195-201
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.