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Purification of an Class Glutathione S-Transferase from Melphalan-resistant Chinese Hamster Ovary Cells and Demonstration of Its Ability to Catalyze Melphalan-Glutathione Adduct Formation¹

Leukaemia Research Fund Laboratory, 4th Floor, Cookson Building, Medical School, Framlington Place, University of Newcastle Upon Tyne, NE2 4HH [A. G. H., E. M., S. A. F., L. H.], and Imperial Cancer Research Fund, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU [I. D. H.] United Kingdom

We have shown previously that a Chinese hamster ovary cell line (designated CHO-Chl^r), generated by exposure to chlorambucil and demonstrating a greater than 20-fold collateral resistance to melphalan, showed increased expression of an form of glutathione S-transferase (GST) associated with amplification of GST genes. Here, we demonstrate that GST purified from CHO-Chl^r 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 class GST may be directly responsible for the development of resistance to bifunctional alkylating agents.

¹ This work was supported by the Leukaemia Research Fund.

² To whom requests for reprints should be addressed.

Received 3/29/94. Accepted 5/23/94.

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