Role of mitotic activity in target tissues in N-nitrosodiethylamine carcinogenesis.
The purpose of this investigation was to study the relationship between cell proliferation in different tissues (liver, lung, spleen, forestomach) and tumour development in C3HA mice treated with a single dose of N-nitrosodiethylamine (NDEA). Cell proliferation was modified by treatment with carbon tetrachloride and dexamethasone in different combinations. Nine experimental groups of mice (total, 454) were studied within 56 weeks. DNA synthesis was determined by liquid scintillation and autoradiography. The mitotic index of tissues was also determined. A close relationship was found between cell proliferative activity in liver and hepatoma incidences; also, long-term proliferation was more effective than short-term, apart from very intensive regeneration of liver at the moment of NDEA administration. Lung tissue of C3HA mice was most sensitive to the action of a single dose of NDEA, and pulmonary tumours were seen frequently in treated animals, independent of the level of cell proliferation in the lungs at the moment of NDEA administration. The results indicate that cell proliferation probably plays different roles in carcinogenesis, but first favours tumour development in tissues that are less sensitive to the direct action of a carcinogen or its metabolites.
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000633:toxicity; D004052:Diethylnitrosamine / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000187:drug effects*; D009602:Nitrosamines / Q000633:toxicity*
D009602:Nitrosamines; D004052:Diethylnitrosamine; D003907:Dexamethasone; D004247:DNA; D002251:Carbon Tetrachloride