GENOTOXICITY AND CELL PROLIFERATIVE ACTIVITY OF 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE [MX] IN RAT GLANDULAR STOMACH

MX is a strong direct acting mutagen on Salmonella typhimurium TA1OO and is present in chlorinated tap water which contains organic compounds. MX was administered orally to 7-week-old male F344 rats, and its genotoxicity in the pyloric mucosa of stomach was examined by analysis of DNA single strand scissions by the alkaline elution method. The effect of MX on cell proliferation was examined by assays of the inductions of replicative DNA synthesis and ornithine decarboxylase. MX at doses of 20-48 mg/kg body weight induced DNA single strand scissions dose-dependently (p<0.02) in the pyloric mucosa of the stomach 2 h after its administration. Moreover at doses of 10-60 mg/kg body weight, it induced up to 21-fold increase in replicative DNA synthesis (p<0.01) 16 h after its administration. At doses of 10-60 mg/kg body weight, it induced up to 100-fold increase in ornithine decarboxylase activity with a maximum 16 h after its administration. These results suggest that MX is genotoxic and induces cell proliferation in the glandular stomach of rats.