title: Glutathione S-transferase activity, sulfhydryl group and glutathione levels, and DNA cross-linking activity with chlorambucil in chronic lymphocytic leukemia.
abstract: Glutathione (GSH) levels and glutathione S-transferase (GST) activities were measured in the leukemia cells of 12 patients with chronic lymphocytic leukemia. Both were correlated with prior clinical exposure to alkylating agents and with DNA cross-link formation by chlorambucil in these cells in vitro. No correlation was observed between prior exposure to alkylating agents and GSH level or GST activity. An inverse correlation was observed between GST activity and cross-linking by chlorambucil, which was enhanced if both GST activity and GSH level were related to cross-linking. These findings suggest that the combination of GST and GSH protects the DNA of leukemia cells from chlorambucil, but the role of this combination in clinical resistance remains to be determined.
authors.affiliation: Manitoba Cancer Treatment and Research Foundation, Winnipeg, MB, Canada.
authors.forename: J B
authors.initials: JB
authors.lastname: Johnston
authors.forename: L G
authors.initials: LG
authors.lastname: Israels
authors.forename: G J
authors.initials: GJ
authors.lastname: Goldenberg
authors.forename: C D
authors.initials: CD
authors.lastname: Anhalt
authors.forename: L
authors.initials: L
authors.lastname: Verburg
authors.forename: M R
authors.initials: MR
authors.lastname: Mowat
authors.forename: A
authors.initials: A
authors.lastname: Begleiter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002699:Chlorambucil / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm / Q000187:drug effects*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D013438:Sulfhydryl Compounds; D002699:Chlorambucil; D005982:Glutathione Transferase; D005978:Glutathione