Tissue-specific induction of mutations by acute oral administration of N-methyl-N'-nitro-N-nitrosoguanidine and beta-propiolactone to the Muta Mouse: preliminary data on stomach, liver and bone marrow.
We used the positive selection Muta 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 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 Mouse model can be used to predict the gastric specificity of genotoxic carcinogens.
Brault
D
D
Rhône-Poulenc Rorer, Drug Safety Department, Vitry sur Seine, France.
Bouilly
C
C
Renault
D
D
Thybaud
V
V
D000284:Administration, Oral; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D004260:DNA Repair; D008099:Liver / Q000187:drug effects*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D011420:Propiolactone / Q000008:administration & dosage / Q000633:toxicity*; D013270:Stomach / Q000187:drug effects*
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D011420:Propiolactone