INTERACTION OF C-14-LABELED FUMONISIN-B MYCOTOXINS WITH PRIMARY RAT HEPATOCYTE CULTURES

An in vitro study on the interaction and biotransformation of the [C-1 4]fumonisin B mycotoxins was conducted, using primary rat hepatocyte c ultures and subcellular enzyme preparations. At the same concentration , fumonisin B-2 (FB2) exhibited a higher cytotoxicity and specific bin ding to primary rat hepatocytes than fumonisin B-1 (FB1). However, if the effective dose level (EDL) is considered (i.e. the lowest level of toxin that binds to the hepatocytes to elicit a cytotoxic effect), FB 1 and FB2 exhibited a similar cytotoxic effect. FB1 was found to be as sociated with both the soluble and insoluble compartments within the c ell. As assessed by the radioactivity associated with the cellular pre parations, very little (approximately 0.01%) FB1 and/or FB2 bound to h epatocytes. In the subsequent fractionation of the culture medium usin g amberlite XAD-2 and silica-gel chromatography, no metabolites were d etected, indicating that the fumonisin molecule was not metabolized by primary hepatocytes. The latter aspect was confirmed by the fact that incubation of FB1 with microsomal enzyme preparations also failed to indicate any metabolism of the fumonisins by the esterases or by cytoc hrome P-450 monooxygenase. FB1 was also found not to be a substrate fo r the triglyceride hepatic endothelial lipase, nor for a lipase from p orcine pancreas. This study supports further the hypothesis that the i ntact molecule of the fumonisins is required for biological activity.