Cell cycle-dependent effects of wortmannin on radiation survival and mutation

Wortmannin, a known radiation sensitizer, has been used in experiments with synchronized cells to compare its effect on radiation survival and mutatio n induction within the cell cycle. PL61 cells (CHO cells with an inactivate d HPRT gene containing a single active copy of a bacterial gpt gene) were s ynchronized by mitotic selection. Wortmannin administered before gamma irra diation caused a greater sensitization in G(1)-phase cells relative to late S/G(2)-phase cells. Preferential radiosensitization of G(1)-phase cells by wortmannin sets a limit to the proposed use of wortmannin in radiation the rapy, since, in contrast to normal tissues, tumors usually have high propor tions of S-phase cells. Wortmannin increased mutation frequencies in both G (1)- and S/G(2)-phase cells. Interestingly, relative increases in radiation -induced mutations in G(1) and S/G(2) phases were comparable. The results a re discussed in terms of the contributions of different repair modes in the production of mutations. (C) 2001 by Radiation Research Society.