Inhibition of protein synthesis in rat primary hepatocytes by extracts of Fusarium moniliforme-contaminated corn.

Mycological screening of two separate lots of corn samples that caused field cases of equine leukoencephalomalacia (ELEM) revealed heavy contamination with the fungus Fusarium moniliforme. Neutral and acidic fractions of a chloroform-methanol (1:1, v/v) extract of the corn were evaluated for toxicity using rat primary hepatocytes. The extracts had little effect on the release of lactate dehydrogenase from the hepatocytes, and were without effect on unscheduled DNA synthesis, indicating low cell lethality and lack of genotoxicity. However, neutral extracts of the corn were found to contain potent inhibitor(s) of protein synthesis as measured by incorporation of [3H]valine into the hepatocytes. When an isolate of F. moniliforme obtained from the corn samples or an isolate of F. moniliforme from South Africa that had previously been shown to cause ELEM (MRC 826) were grown on autoclaved seed corn, neutral extracts of the culture materials similarly inhibited protein synthesis. Whether the compound(s) responsible for inhibition of protein synthesis is associated with any of the toxic syndromes associated with F. moniliforme remains to be determined. The use of primary hepatocytes may be a useful bioassay for elucidating biologically active secondary metabolites of fungi.