A noncarcinogenic small dose of n-methylnitrosourea enhances colon tumorigenesis in F344 rats.

摘要

Very small amount of carcinogens such as nitroso compounds and heterocyclic amines has been found in human feces. This study was designed to investigate in F344 rats whether an intrarectal noncarcinogenic small dose of n-methylnitrosourea (0.2 mg, 3 times weekly) affects colon carcinogenesis initiated with an intrarectal large dose (2 mg, 3 times weekly) of this carcinogen. The colon tumor yield at week 50 in 12 rats receiving the large dose for 2 weeks and then the small dose for the next 30 weeks significantly increased as compared to 23 rats receiving only the large dose for 2 weeks: 100% vs. 70% in tumor incidence and 4.3 vs. 1.2 in mean number of tumors per rat. No tumors were found in 12 rats receiving only the small dose for 30 weeks. The results indicate that a very small amount of carcinogens could participate in a tumor-enhancing effect on the high-risk colon induced with a large dose of carcinogens, even though their less amounts insufficient to complete carcinogenesis process. Further studyis needed to elucidate if administration of such a small dose could induce epigenetic alterations or further genetic changes in the initiated colonic cells.