Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells - PubMed (original) (raw)

. 1995 Apr 15;55(8):1639-42.

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Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells

K J Russell et al. Cancer Res. 1995.

Abstract

We have examined the effect of abrogation of the G2 checkpoint on the radiosensitivity of G1 checkpoint-proficient and G1 checkpoint-deficient cells. A549 human lung adenocarcinoma cells were transduced with the E6 oncogene of the human papillomavirus type 16 to eliminate their radiation-induced G1 arrest. These E6+ cells exhibited a dose-dependent increase in radiation resistance compared to control A549 cells transduced with the vector alone. Treatment (96 h) with 2 mM caffeine resulted in an abrogation of the cellular G2 checkpoint in both E6+ and control cells and a differential radiosensitizing effect on the two cell lines such that the E6+ clones and the vector controls became equally radiosensitive. These data show that human tumors which are radioresistant due to the loss of the p53-mediated G1 checkpoint can be made radiosensitive by abrogation of the G2 checkpoint. The implications of these results for cancer therapy are discussed.

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