Cell cycle variations in azoxymethane-induced rat colorectal carcinogenesis studied by flow cytometry

Cell cycle variations and DNA aneuploidy, were investigated in different ph ases of azoxymethane (AOM)induced colon carcinogenesis in rats by flow cyto metry. K-ras gene mutations (transitions G-A) were frequently detected in a berrant crypt foci (ACF) initial pre-neoplastic lesions. The fraction of ce lls in the G2M-phase of the cell cycle was higher in ACF compared to the no rmal mucosa of control rats. A similar modification of the cell cycle was f ound in adenomas and adenocarcinomas but, unexpectedly, also in morphologic ally normal mucosa from AOM-treated animals indicating that AOM treatment p ermanently modifies cell cycle control in rat colon mucosa. These alteratio ns, however, were not associated with DNA aneuploidy as reported in human s poradic colorectal cancer, suggesting that tumour development in AOM-treate d rats is less dependent on aneuploidy.