A COMPARATIVE-STUDY OF OCHRATOXIN A-INDUCED APOPTOSIS IN HAMSTER-KIDNEY AND HELA-CELLS

Ochratoxin A (OA), produced by strains of Aspergillus and Penicillium, at a dose of 20 mu g/ml caused nuclear and nucleolar changes characteristic of apoptosis in hamster kidney (HaK) and HeLa cells. However, the morphological and biochemical lesions were not identical in the two cell types. In HaK cells micronuclei formation in prophase and interphase cells predominated but in HeLa cells apoptotic body formation was more prevalent. Indirect immunofluorescence indicated that nucleolar morphology was affected in both cell types with segregation of the fibrillar and granular components of the nucleolus present after 24 hr exposure. [S-35]Methionine incorporation into SDS-PAGE-separated proteins was decreased after continuous exposure for 24 hr, but after only 3 hr exposure, the synthesis of three proteins was markedly increased in HaK (approximate to 39, 90, and 180 kDa) and HeLa (approximate to 40, 92, and 150 kDa) cells. Enhanced early synthesis of proteins was more pronounced in HaK cells in the G(1)-phase and in HeLa cells in the S-phase. Internucleosomal DNA breaks, characteristic of apoptosis, were present in G(1) and S-phase HaK cells exposed to OA. In contrast, DNA of very high molecular weight was seen in synchronized HeLa cells. The results indicate that OA may activate different cellular processes involved in the degradation of DNA in HaK and HeLa cells. (C) 1994 Academic Press, Inc.