INCREASED CYTOTOXICITY OF RICIN IN A PUTATIVE GOLGI-DEFECTIVE MUTANT OF CHINESE HAMSTER OVARY CELL

We have studied the cytotoxicity of ricin in a monensin-resistant mutant (MonR-31) of Chinese hamster ovary (CHO) cell line which is presumably altered in Golgi functions/structures. The cytotoxicity of ricin was increased in MonR-31 mutant cells compared with that in its parental CHO cells. In wild-type CHO cells, the cytotoxicity of ricin was enhanced by NH4Cl, bafilomycin A1, or nigericin. The enhancement of ricin cytotoxicity by these compounds was greatly reduced in MonR-31 mutant cells. Brefeldin A (BFA), which disrupts the structure of the Golgi apparatus, inhibits the cytotoxicity of ricin in both CHO and MonR-31 cells. We have also examined the effects of glycosylation inhibitors and the removal of high mannose oligosaccharide chains in ricin on the ricin hypersensitivity in MonR-31 cells. The hypersensitivity of MonR-31 cells to ricin is apparently not due to any difference in glycosylation between CHO and MonR-31 cells or in the processing of oligosaccharides on ricin by the target cells. Nigericin at low concentration (10 nM), which has no effect on the cytotoxicity of diphtheria toxin, enhances the ricin cytotoxicity, but inhibits the modeccin cytotoxicity. Our results suggest that important step(s) in the intoxication process of CHO cells by ricin and modeccin take place in the Golgi region. © 1990.