Mutagenicity and toxicity of the DNA alkylation carcinogens 1, 2-dimethylhydrazine and azoxymethane in Escherichia coli and Salmonella typhimurium

DNA alkylating agents such as 1, 2-dimethylhydrazine (SDMH)and azoxymethane (AOM) are potent carcinogens and are widelyused to induce colon tumors in experimental animals. However,standard bacterial mutagenesis assays have failed to detectthe mutagenic effects of these chemicals. Using derivativesof a set of Escherichia coli test strains developed by Cupplesand Miller (Proc. NatL Acad. Set USA, 86, 5345, 1989), we havedemonstrated that under two conditions, SDMH and AOM inducedpoint mutations by several-fold in a dose-dependent manner:(i) of six possible base substitutions, they only induced GC