Effects of paraquat on macromolecule synthesis in cultured pneumocytes.

Abstract

The effects of paraquat (PQ) on cell growth, DNA, RNA and protein synthesis and on superoxide dismutase (SOD) activity were investigated in cultured pneumocytes of type II cell origin and human embryonic fibroblast cells of the lung. The incorporation of 3H-thymidine, 3H-uridine and 14C-leucine into DNA, RNA and protein, respectively, were all reduced to 25%-70% of the control by PQ at 10(-3) M, but not at 10(-5) M nor 10(-7) M. The activity of SOD in the cells was increased to 130%-270% by 10(-3) M of PQ. Among the cells studied, A-549 cells, which were most resistant to the inhibitory effect of PQ on cell growth and the synthesis of DNA, RNA and protein had the highest induction of SOD activity by PQ. In contrast, L-2 cells in which the cell growth and the synthesis of nucleic acids and protein were most inhibited had the lowest induction of SOD activity by PQ. These results indicate that nucleic acids and protein synthesis are possible targets for lethal effects of PQ in the pulmonary cells, and that the specificity of PQ toxicity in pulmonary cell lines might be related to the ability of induction of SOD by PQ.