EFFECTS OF POTASSIUM DICHROMATE ON NUCLEIC-ACID AND PROTEIN SYNTHESES AND ON PRECURSOR UPTAKE IN BHK FIBROBLASTS

Abstract

Treatments for 1-4 h with the carcinogen 10-4 M potassium dichromate, a soluble hexavalent Cr salt with a strong oxidizing power, markedly reduce DNA and RNA accumulation rates in hamster kidney fibroblasts grown in vitro (BHK line), as shown by quantitative spectrophotometric determinations. Such inhibitory action is not immediately evident on the basis of the incorporation rates of labeled nucleosides into DNA and RNA, as dichromate also affects the relative concentrations of labeled precursors in the intracellular pool. Dichromate stimulates and then inhibits nucleoside (mostly thymidine) uptake, whereas amino acid uptake is immediately inhibited. Actual rates of macromolecular syntheses were calculated by taking into account the induced changes of soluble precursor concentrations. Such normalized rates show that dichromate induces a sudden blockage of DNA replication, whereas RNA and protein syntheses are secondarily inhibited. The observed cytotoxic effects of dichromate are tentatively referred to the oxidation of cell components by hexavalent Cr and thereby to the interaction of reduced trivalent Cr with specific biological ligands on cell membrane and DNA.