The effects of supranormal temperature on the activity of poly(ADP-ribose) glycohydrolase were studied by assaying the enzyme in cell extracts derived from cells subjected to hyperthermia and comparing with extracts that were heated in vitro. The enzyme activity was reduced by both hyperthermic treatment of cells and by heating of cell extracts; however greater reductions were observed when intact cells were subjected to hyperthermia. The additional reduction observed when intact cells were heated was reversed when cells were allowed to recover at 37°C following hyperthermia. We postulate that hyperthermia alters poly(ADP-ribose) glycohydrolase activity by two mechanisms, an irreversible thermal denaturation of the enzyme and a reversible metabolic alteration. Changes in poly(ADP-ribose) glycohydrolase activity can account in full for the observed alterations of poly(ADP-ribose) metabolism that occur following hyperthermia.

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This work was supported in part by grants from the NIH (CA43894); The Medical Research Council, Stockholm, Sweden; The Medical Faculty, University of Lund, Lund, Sweden; The Anna Cederbergs Foundation for Medical Research, Karolinska Institute, Stockholm, Sweden; The John and Augusta Persson's Foundation for Medical Research, Lund, Sweden; and The Medical Research Council of Canada and National Research Council of Canada.

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©1988 American Association for Cancer Research.
1988
American Association for Cancer Research, Inc.