The role in cancer therapy of inhibiting recovery from PLD induced by radiation or bleomycin.

Effects on survival of allowing and inhibiting potentially lethal damage recovery (PLDR) after X ray or bleomycin (bleo) exposure, especially at clinically applicable doses, were examined in plateau phase Chinese hamster ovary (CHO) cells. Dose modifying factors (DMF's) between immediately explanted cells and those trypsinized 24 hours after various doses of X rays were 2.51 +/- 0.12 (mean +/- 2 S.E.) at 70% surviving fraction (SF), 2.03 +/- 0.085 at 40% and 1.71-1.79 at lower SF levels. Thus, at doses used clinically (1-4 Gy), the DMF by PLDR was more than 2.0, suggesting its importance in radiotherapy of cancers. Feeder layers were found to increase the SF, especially for replating immediately after bleo exposure. Among the inhibitors tested, 3'-deoxyguanosine at 3.7 mM and caffeine at 10.3 mM inhibited x and bleo PLDR (DMF of 1.0-1.2) when trypsinized 24 hours after treatment. However, interestingly, 3 aminobenzamide, a specific inhibitor of poly (ADP) ribose synthesis, even at 14.7 or 29.4 mM, was not as effective in suppressing both x and bleo PLDR, suggesting the role of repair processes independent of poly (ADP) ribose levels in PLDR in plateau phase cultures. Possibilities of clinical application of PLDR inhibitors as radio- and chemosensitizers are discussed.