GENOTOXIC EFFECTS OF 3 FUSARIUM MYCOTOXINS, FUMONISIN-B-1, MONILIFORMIN AND VOMITOXIN IN BACTERIA AND IN PRIMARY CULTURES OF RAT HEPATOCYTES

The genotoxic effects of three widespread Fusarium toxins, vomitoxin ( VOM), moniliformin (MON) and fumonisin B-1 (FB1) were investigated in bacterial tests and in micronucleus (MN) and chromosomal aberration (C A) assays with primary rat hepatocytes, All three toxins were devoid o f activity in gene mutation assays with Salmonella typhimurium strains TA98 and TA100 and in SOS chromotests with E. coli strain PQ37 in the presence and absence of metabolic activation, FB1 and VOM gave negati ve results in differential DNA repair assays with E. coli K-12 strains (343/753, uvrB/recA and 343/765, uvr(+)/rec(+)); with MON, a marginal effect was seen in the absence of metabolic activation mix at relativ ely high concentrations (greater than or equal to 55 mu g/ml). In meta bolically competent rat hepatocytes stimulated to proliferate with EGF and subphysiological Ca2+ concentrations, a decrease of cell division was observed with all three toxins at concentrations greater than or equal to 10 mu g/ml, VOM was strongly cytotoxic at 100 mu g/ml. All th ree mycotoxins caused moderate increases of the MN frequencies at low concentrations (less than or equal to 1 mu g/ml), but no clear dose-re sponse effects were seen and at higher exposure levels the MN frequenc ies declined. In the CA experiments with hepatocytes, pronounced dose- dependent effects were observed with all three toxins. MON caused a 9- fold increase over the spontaneous background level after exposure of the cells to 1 mu g/ml for 3 h, with FB1 and VOM, the increases were 6 - to 7-fold under identical experimental conditions. This is the first report on clastogenic effects of VOM and FB1 in mammalian cells, with MON induction of CAs in V-79 cells has been described earlier. Since all three mycotoxins caused CAs at very low concentration levels in li ver cells in vitro, it is possible that such effects may also occur in humans and mammals upon consumption of Fusarium-infected cereals.