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JNCI Journal of the National Cancer Institute 1990 82(9):776-779; doi:10.1093/jnci/82.9.776
© 1990 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 82, No. 9, 776-779, May 2, 1990
© 1990 Oxford University Press

Glutathione S-Transferase Activity, Sulfhydryl Group and Glutathione Levels, and DNA Cross-Linking Activity With Chlorambucil in Chronic Lymphocytic Leukemia

James B. Johnston*, Lyonel G. Isrels, Gerals J. Goldenberg, Cynthia D. Anhalt, Linda Verburg, Michael R. A. Mowat, Asher Begleiter

Manitoba Cancer Treatement and Research Foundation Winnipeg, MB, Canada
Department of Internal Medicine, University of Manitoba Winnipeg, MB, Canada
Department of Physiology, University of Manitoba Winnipeg, MB, Canada
Department of Pharmocology and Therapeytics, University of Manitoba Winnipeg, MB, Canada

*Correspondence to: James B. Johnston, M.D., Department of Internal Medicine, University of Manitoba, 100 Olivia St., Winnipeg, MB, R3E OV9 Canada

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. (J Natl Cancer Inst 82: 776–779, 1990)


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