Purification of an alpha class glutathione S-transferase from melphalan-resistant Chinese hamster ovary cells and demonstration of its ability to catalyze melphalan-glutathione adduct formation
Hall, A.G.; Matheson, E.; Hickson, I.D.; Foster, S.A.; Hogarth, L.
Cancer Research 54(13): 3369-3372
1994
ISSN/ISBN: 0008-5472 PMID: 8012951 Document Number: 423119
We have shown previously that a Chinese hamster ovary cell line (designated CHO-Chlr), generated by exposure to chlorambucil and demonstrating a greater than 20-fold collateral resistance to melphalan, showed increased expression of an alpha form of glutathione S-transferase (GST) associated with amplification of GST genes. Here, we demonstrate that GST purified from CHO-Chlr cells contains a form with a pI of 9, not present in CHO-K1 cells or Chinese hamster liver, which has the ability to accelerate the formation of glutathione-melphalan adducts. This result provides evidence that overexpression of the alpha class GST may be directly responsible for the development of resistance to bifunctional alkylating agents.