Distribution and binding of the carcinogens 1-methyl-1-nitrosourea and 1-methyl-3-nitro-1-nitrosoguanidine in the guinea pig after oral administration.
Guinea pigs were given radioisotopic 1-methyl-1-nitrosourea (MNU) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) as a single oral dose of 0.1 mmol/kg and uptake into TCA-precipitable material, whole tissue protein and 7-methyl-guanine and O6-methylguanine were determined in brain, kidney, liver, pancreas, small intestine and stomach after 2, 4 and 24 h. The labeling of TCA-precipitable material and the formation of methylated bases by methyl-labelled MNU clearly exceeded that by MNNG in extra-intestinal tissues such as brain, liver, kidney and pancreas. In the stomach, there was greater DNA methylation by MNNG than by MNU. Labelling of TCA-precipitable material and whole tissue protein by the carbonyl group of MNU was greater than that by the guanidino group of MNNG in brain, liver, kidney and pancreas, while MNNG exceeded MNU in the stomach. These data are consistent with the concept that orally administered MNU would be an effective carcinogen in extra-intestinal tissues, while MNNG would be a locally acting gastric carcinogen.
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D006168:Guinea Pigs; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage / Q000378:metabolism*; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000378:metabolism*; D009607:Nitrosourea Compounds / Q000378:metabolism*; D011485:Protein Binding; D014018:Tissue Distribution
D009607:Nitrosourea Compounds; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea