A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowel

摘要: The ability of four mutagenic/carcinogenic chemicals administered as single doses to induce a programmed form cell death (apoptosis) in the BDF1 mouse large bowel was studied and compared with previous study on small intestine using same mice. number apoptotic cells counted following treatment direct-acting agents N-nitroso-N-methylurea (NMU) N-nitroso-N-ethylurea (NEU) two which require metabolic activation 1,2-dimethylhydrazine (DMH) N-nitrosodimethylamine (NDMA). DMH (80 mg/kg) most effective at inducing acute this closely followed by NMU (200 mg/kg). least agent NDMA. peak yield apoptosis occurred between 4 h 8 after treatment. An analysis changing shapes frequency plots each position crypt various times exposure permits an estimate be made primary target for cytotoxic action time t = 0. For studied, is range 5th 10th from base crypt. This distribution not coincident that presumptive stem cells, 1 or 2. Comparisons results previously obtained (ileum) mice show relative effectiveness differs. Furthermore, about 4th bottom ileum, here presumed cells. Our interpretation data damaged region are removed suicide programme, effectively removes potentially harmful genetic alterations. In contrast, bowel, initiated particularly strongly but tends occur higher absence selective deletion process may result perpetuation deleterious mutations colonic population explain part, incidence cancers observed bowel.