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-spe cific activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and beta -propiolactone (BPL), two highly reactive alkylating agents known to i nduce genetic damage and tumors in rodent stomach when administered or ally. 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 stom ach increased significantly by 6.4-fold and 8.8-fold, respectively. A slight (1.8-fold) but significant increase in mutation frequency was a lso 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 anima ls. These data indicate that the Muta(TM)Mouse model can be used to pr edict the gastric specificity of genotoxic carcinogens.