DNA FRAGMENTATION IN MOUSE GASTRIC EPITHELIAL-CELLS BY PRECARCINOGENS, ULTIMATE CARCINOGENS AND NITROSATION PRODUCTS - INDICATOR FOR DETERMINATION OF ORGANOTROPY AND METABOLIC ACTIVATION

The feasibility of using alkaline sucrose gradient analysis of the digestive tract tissue of mice to uncover the carcinogenic capacity of organotropic compounds was examined. Young Swiss mice were injected with 3H-TdR [thymidine] to label the DNA of the epithelial cells of the digestive tract. They were force-fed carcinogenic and noncarcinogenic chemicals 30 h later. Tissue samples were taken 4 h posttreatment and hydrolized on top of the alkaline sucrose gradient. Shifts in sedimentation profiles indicated that: the carcinogens 4-nitroquinoline-1-oxide (4NQO) and 6-methyl 4NQO cause DNA fragmentation in the epithelial cells of esophagus, cardiac and pyloric stomach, while the noncarcinogen 6NQO lacks this capacity; the ultimate carcinogen N-acetoxy-2AAF [acetylaminofluorene] caused DNA fragmentation in esophagus and stomach cells, whereas the precarcinogen 2-AAF exerted no detectable effect; only carcinogenic nitrosation products of MG [methylguandidine] damaged the DNA; and the precarcinogens 2-AAF and DMN [dimethylnitrosamine] elicited DNA fragmentation in their main target organ, the liver, but had no effect on the epithelial cells of esophagus and stomach. The results suggest that the application of the sucrose gradient technique to the epithelial cells of esophagus, stomach and liver of prelabeled (3H-TdR) and force-fed young mice incorporates the advantages of in vitro short-term bioassays with the completeness of tests using whole mammals.