A DNA double-strand break repair-deficient mutant of CHO cells shows reduced radiosensitization after exposure to hyperthermic temperatures in the plateau phase of growth

Abstract

Heat response and heat-induced radiosensitization were studied in plateau-phase cultures of CHO cells and their radiation-sensitive counterpart, the xrs-5 cells. The xrs-5 cells were more sensitive to heat alone than were CHO cells. A large enhancement in radiation-induced killing was observed in CHO cells pre-exposed to heat (43°C), expressed as a reduction in the values of D_o and D_q. Contrary to the results obtained with CHO cells, pre-exposure to heat of xrs-5 cells affected radiation sensitivity to a much lesser extent. D_I, the radiation dose required to reduce cell survival to 1%, decreased in CHO cells from 8ċ7 Gy to 2ċ5 Gy with increasing heat damage (cell survival after exposure to heat alone), whereas it decreased from 1ċ4 Gy to 0ċ9 Gy in xrs-5 cells. These results suggest that heat-induced radiosensitization is compromised in plateau-phase xrs-5 cells. Since xrs-5 cells are deficient in DNA dsb repair, it is hypothesized that DNA dsb repair proficiency is a prerequisite for heat radiosensitization and that heat-induced inhibition of DNA dsb repair is likely to contribute to the radiosensitization observed in repair-proficient cell lines after exposure to high temperatures.

Key Words:

• hyperthermia
• radiation
• radiosensitization
• DNA double-strand breaks
• CHO cells
• xrs-5 cells