INVITRO MUTAGENIC ACTIVITY OF 5-(3,3-DIMETHYL-1-TRIAZENO)-IMIDAZOLE-4-CARBOXAMIDE (DTIC) IN EUKARYOTIC AND PROKARYOTIC CELLS

The in vitro mutagenic activity of [the antineoplastic drug] 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) was studied in bacteria [Escherichia coli, Salmonella typhimurium] and Chinese hamster [lung V79] cells with and without metabolic activation by rat liver microsomes. DTIC was highly mutagenic in the 2 systems. DTIC in the prokaryotic systems did not require metabolic activation to be effective. By comparing the mutagenic activity on bacteria of DTIC and of its monomethyl- and hydroxymethyl-derivatives (MIC [5-(3-methyltriazeno)-imidazole-4-carboxamide] and HMIC [5-(3-hydroxymethyl-3-methyl-1-triazeno)-imidazole-4-carboxamide]), MIC and HMIC are shown to display a pattern of mutagenicity different from DTIC. MIC and/or HMIC are probably not metabolites directly responsible for the mutagenic activity of DTIC in bacteria.