Increased glutathione-S-transferase activity in a cell line with acquired resistance to nitrogen mustards.

A Walker 256 rat mammary carcinoma cell line (WR) resistant to bifunctional nitrogen mustards has been shown to have an approximate twofold increase in bulk glutathione-S-transferase activity compared to the parent cell line. Substrate specificity studies suggest that higher levels of Yb subunit contribute to the increased activity. By exposing WR cells to additional chlorambucil, either as a single concentration (50 micrograms/ml) or at 5 micrograms/ml for 10 days, transferase activity was further increased by up to three times the normal WR level. By using colony-forming assays, mitotic index depression, or trypan blue exclusion, the increased transferase activity could be correlated with an increase in resistance of these cells to either subsequent chlorambucil or a different bifunctional nitrogen mustard, phosphoramide mustard.