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.
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.
Hall
A G
AG
Leukaemia Research Fund Laboratory, Medical School, University of Newcastle Upon Tyne, United Kingdom.
Matheson
E
E
Hickson
I D
ID
Foster
S A
SA
Hogarth
L
L
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology*; D006224:Cricetinae; D004351:Drug Resistance; D005982:Glutathione Transferase / Q000737:chemistry / Q000302:isolation & purification*; D008099:Liver / Q000201:enzymology; D008558:Melphalan / Q000494:pharmacology; D008969:Molecular Sequence Data
D005982:Glutathione Transferase; D008558:Melphalan