Tissue-specific induction of mutations by acute oral administration of N-methyl-N'-nitro-N-nitrosoguanidine and beta-propiolactone to the Muta(TM)Mouse: Preliminary data on stomach, liver and bone marrow

We used the positive selection Muta(TM)Mouse model to detect organ-specific activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and beta-propiolactone (BPL), two highly reactive alkylating agents known to induce genetic damage and tumors in rodent stomach when administered orally. Seven days after a single oral administration of MNNG (100 mg/kg) or BPL (150 mg/kg), the mutation frequency in the Muta(TM)Mouse stomach increased significantly by 6.4-fold and 8.8-fold, respectively. A slight (1.8-fold) but significant increase in mutation frequency was also observed in the livers of BPL-treated mice, but not in the livers of MNNG-treated mice or the bone marrow of MNNG- and BPL-treated animals. These data indicate that the Muta(TM)Mouse model can be used to predict the gastric specificity of genotoxic carcinogens.