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.
Leukaemia Research Fund Laboratory, Medical School, University of Newcastle Upon Tyne, United Kingdom.
A G
AG
Hall
E
E
Matheson
I D
ID
Hickson
S A
SA
Foster
L
L
Hogarth
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