TOXICITY OF PRECOCENE-II IN RAT HEPATOCYTE CULTURES - EFFECTS OF SERUM AND CULTURE TIME

Omission of Serum from culture medium markedly increased the toxicity of the cytochrome P450-activated toxin precocene II in 24-h cultures o f rat hepatocytes. In addition, the depletion of glutathione and inhib ition of cytochrome P450 in 24-h cultures increased and decreased, res pectively, the toxicity of precocene II, as seen in vivo. Precocene II was also toxic to 72-h cultures, although the effect of the serum-fre e medium was attenuated. However, depletion of glutathione and inhibit ion of P450 had little or no effect on the toxicity in 72-h cultures. Therefore, the mechanism of precocene II-induced cell death appears to change with time in culture.