EFFECT OF FUMONISIN-B-1 ON PROTEIN AND LIPID-SYNTHESIS IN PRIMARY RATHEPATOCYTES

The effect of fumonisin B-1 (FB1) on protein and lipid synthesis was e valuated in primary rat hepatocytes. FB1 did not affect incorporation of [H-3]leucine into hepatocytes at either non-toxic (150 mu M) or cyt otoxic (500 mu M) concentrations indicating that proc-in synthesis was not affected. However, FB1 significantly (P < 0.01 to P < 0.0001) inh ibited incorporation of [C-14]palmitic acid into hepatocyte cultures i mplying that lipid synthesis was altered. Incorporation of the radiola bel was significantly (P < 0.05 to P < 0.0001) lowered in triacylglyce rol (TAG) and sphingomyelin fractions and increased in phosphatidylcho line (PC) and phosphatidylethanolamine (PEA) in both FB1 concentration s. The incorporation pattern of [C-14]palmitic acid closely resembles the changes in phospholipid levels in the treated cells. The sphingoli pid, sphinganine (Sa), was significantly (P < 0.0001) increased in tre ated cells but there was no significant difference between the toxic a nd non-toxic dose levels implying that the increased Sa level alone is not responsible for the in vitro toxicity. FB1 significantly (P < 0.0 1 to P < 0.001) decreased the level of free cholesterol within the cel l, resulting in an increased PC:cholesterol ratio suggesting a more ri gid membrane structure. Subsequent studies on the fatty acid (FA) prof iles in PC and the neutral lipid, TAG, indicated that FB1 significantl y (P < 0.05 to P < O.0001) increased the levels of the polyunsaturated FAs C18:2n-6 and C20:4n-6 at both concentrations. The FB1-induced cha nges to cellular membranes, specifically those related to FA changes i n the major membrane phospholipids, and the altered FA content of the hepatocytes are likely to be key events in explaining the cytotoxic ef fects and altered growth responses induced by fumonisins in primary he patocytes. (C) 1996 Elsevier Science Ltd. All rights reserved.