Effects of cadmium on glutathione metabolism in cadmium sensitive and cadmium resistant Chinese hamster cell lines.

Three cadmium resistant sublines, Cdr20F4, Cdr30F9, and Cdr200T1, resistant to 26, 40, and 145 micron CdCl2, respectively, have been derived from the cadmium sensitive Chinese hamster cell line CHO (resistant to 0.2 microM CdCl2). The resistance appears to be largely a function of the increased ability of the variant cells to induce the synthesis of metallothioneins (MTs) in response to cadmium, as the incorporation of [35S]cysteine into MTs ranges from an undetectable level to nearly 60% of the total cysteine incorporation into proteins in the CHO and Cdr200T1 cell lines, respectively. Treatment of the cadmium resistant sublines and the parent line with maximal subtoxic levels of Cdcl2 produced increases in the concentration of glutathione and glutathione S-transferase activity. In the parent, cadmium-sensitive CHO cell, the glutathione concentration began to increase after 9 h of exposure to 0.22 microM CdCl2 to over 250% of control level by 12 h. In 1 cadmium resistant line (Cdr20F4) the increase, again at 9 h, was preceded by a decrease, possibly due to depletion of the cysteine pools by the cadmium-induced MT synthesis. The second cadmium-resistant cell line (Cdr30F9) displayed no decrease, and the most cadmium-resistant line (Cdr200T1) showed the decrease and a recovery, but no significant increase by 12 h. In all cell lines there was a small but significant increase in glutathione S-transferase activity by 9 or 12 h. These responses may be specific for the thiol-reactive metal, cadmium, or may represent more general responses to cellular toxicity.