PEROXIDATION OF MEMBRANE-LIPIDS AND OXIDATIVE DNA-DAMAGE BY FUMONISINB-1 IN ISOLATED RAT-LIVER NUCLEI

Fumonisin B-1 (FB1), a contaminant of corn, has been reported to be a hepatocarcinogen in rats. In an attempt to understand its mechanisms o f action, a model system of isolated rat liver nuclei was used to dete rmine what effects, if any, FB1 might have on nuclear membrane lipids and DNA. The data suggested that FB1 induced lipid peroxidation concur rently with DNA strand breaks in this in vitro system. Iron and copper had no statistically significant stimulatory effects on these reactio ns. In addition, the active oxygen scavengers catalase, superoxide dis mutase (SOD), mannitol and sodium azide had no significant inhibitory effects on the FB1-induced DNA strand breaks. However, a small but sig nificant reduction in lipid peroxidation by catalase and mannitol was observed. These results suggested that hydroxyl radicals may be the in itiators of the nuclear membrane lipid peroxidation, which results in production of peroxyl radicals. In turn, the peroxyl radicals may be r esponsible for the DNA strand breaks. An alternative explanation is th at the hydroxyl radicals, produced close to the DNA-bound metal ions, may induce direct site-specific strand breaks, which are insensitive t o the scavengers of active oxygen. (C) 1998 Elsevier Science Ireland L td.