Zinc effects on glutathione metabolism relationship to zinc-induced protection from alkylating agents.

Several aspects of the effects of zinc on the metabolism of glutathione were examined in the Chinese hamster cell (line CHO) and in three derived sublines which differ in their resistance to the thiol reactive heavy metal cadmium. In the parental CHO cell, which does not induce the synthesis of metallothionein in response to zinc, glutathione levels remained approximately constant during the first 6 hr of zinc exposure. In the resistant cell lines, which induce the synthesis of metallothionein in response to zinc, the glutathione levels dropped transiently during zinc exposure. In all cell lines except the most cadmium resistant line, the glutathione levels after 12 hr were increased up to 3-fold relative to pretreatment levels. Similarly, the glutathione S-transferase activity measured by the conjugation of 1-chloro-2,4-dinitrobenzene to glutathione was increased after 9-12 hr of zinc treatment in all except the most highly cadmium resistant cell line. Glutathione reductase was not affected consistently by zinc treatment; however, the level of activity of this enzyme in the most highly cadmium resistant line was two to three times greater than that observed in the other cell lines. These effects are considered in relation to the zinc-induced protection of these cells from the toxic effect of the alkylating agent melphalan.