Copper and zinc toxicity in two rat hepatoma cell lines varying in differentiation.

1. The differentiation status of cells is considered to represent an important factor in determining the effects of toxic components. 2. Two rat hepatoma cell lines, MH1C1 and HTC, were used to study differences in the sensitivity to two toxic metals: copper and zinc. 3. The differentiation of the cell lines was characterized using light microscopy, growth pattern, gamma glutamyltransferase (GGT) activity and albumin production as parameters. 4. The MH1C1 cell line was described to be more differentiated. 5. Albumin production in the MH1C1 cells was significantly higher than in the HTC cells whereas the GGT activity was only slightly different. 6. Toxicity of Cu and Zn was compared. Zn appeared to be more toxic to the cells than Cu, when leakage of lactate dehydrogenase and potassium were measured, whereas both metals were equally toxic when expressed as DNA remaining after 24 hr. 7. The MH1C1 cell line appeared to be more sensitive to Cu and Zn than the HTC. 8. The two metals appeared to have different targets in the cell; Cu may affect the nucleus and Zn the cell membrane.