Alkylation of Ehrlich Ascites Tumor Cells Elicits a Response from Poly(ADP-Ribose) Polymerase
The activity of poly(ADP-ribose) polymerase in Ehrlich ascites tumor cell nuclei is seen to increase in a dose-dependent manner when cells are alkylated 1 hr with 1,3-bis(2-chloroethyl)-1-nitrosourea or nitrogen mustard. Stimulation appeared at drug amounts far in excess of that required for total cell death. At biologically relevant levels of alkylation (LD50) there is no increase in enzyme activity relative to controls seen until repair of DNA is allowed to occur. During repair, enzyme activity reaches a maximum two to four hrs after removal of the drug and returns to control levels after six hrs. Alkaline sucrose gradient centrifugation reveals fragmentation of DNA during the period concomitant with maximum poly(ADP-ribose) polymerase activity and a return to high molecular weight DNA six hrs after removal of the drug.
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