Chernikova, S. B., Lindquist, K. L. and Elkind, M. M. Cell Cycle-Dependent Effects of Wortmannin on Radiation Survival and Mutation. Radiat. Res. 155, 824–829 (2001).

Wortmannin, a known radiation sensitizer, has been used in experiments with synchronized cells to compare its effect on radiation survival and mutation induction within the cell cycle. PL61 cells (CHO cells with an inactivated HPRT gene containing a single active copy of a bacterial gpt gene) were synchronized by mitotic selection. Wortmannin administered before γ irradiation caused a greater sensitization in G₁-phase cells relative to late S/G₂-phase cells. Preferential radiosensitization of G₁-phase cells by wortmannin sets a limit to the proposed use of wortmannin in radiation therapy, since, in contrast to normal tissues, tumors usually have high proportions of S-phase cells. Wortmannin increased mutation frequencies in both G₁- and S/G₂-phase cells. Interestingly, relative increases in radiation-induced mutations in G₁ and S/G₂ phases were comparable. The results are discussed in terms of the contributions of different repair modes in the production of mutations.