ENHANCING EFFECTS OF CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE (MX) ON CELL-PROLIFERATION AND LIPID-PEROXIDATION IN THE RAT GASTRIC-MUCOSA

The influence of hloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, a mutagen in chlorinated water, on cell proliferation and lipid peroxida tion in the glandular stomach mucosa was investigated in male 4-week-o ld Wistar rats. Animals were given 50 p.p.m., 25 p.p.m., 12.5 p.p.m., 6.25 p.p.m. or 0 p.p.m. of MX solution in their drinking water for 5 w eeks. At the end of this period, cell proliferation in the mucosal epi thelia of the gastric fundus was increased in a dose-dependent manner up to 25 p.p.m., at which dose the induction was statistically signifi cant as compared with the control value (P < 0.05). The MX treatment w as also associated with increased lipid peroxidation levels in the gas tric mucosa as well as in the urine, with loose dose-dependence, altho ugh not at 50 p.p.m. Mucosal lipid peroxidation was significantly incr eased in animals given 25 p.p.m. as compared with controls (P < 0.05). Similarly, the levels of urinary lipid peroxidation were significantl y higher in rats given 25 p.p.m. or 12.5 p.p.m. than in the controls ( P < 0.05). Histopathologically, gastric erosion was noted in rats rece iving 25 p.p.m. or more of MX. There were no statistical differences b etween groups for serum biochemical data. The results thus suggest tha t MX may exert a gastric tumor-promoting action in rats, even at low d oses which do not give rise to toxic effects, because of the clear dos e-response relationship evident at low levels.