p27Cip/Kip Is Involved in Hsp25 or Inducible Hsp70 Mediated Adaptive Response by Low Dose Radiation

Thermoresistant (TR) clone of radiation-induced fibrosarcoma (RIF) cells have been reported to show adaptive response to 1 cGy of low dose radiation, and hsp25 and inducible hsp70 are involved in this process. In the present study, to further elucidate the mechanism of how hsp25 and inducible hsp70 regulate the adaptive response, hsp25 or inducible hsp70 overexpressed RIF cells were irradiated with 1 cGy and cell cycle was analyzed. Hsp25 or inducible hsp70 overexpressed cells as well as TR cells showed increase of G1 phase population after gamma-irradiation at 1 cGy, while the parent RIF cells did not. [3H]-Thymidine and BrdU incorporation also indicated that both hsp25 and inducible hsp70 were involved in G1 arrest after 1 cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in hsp25 and inducible hsp70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of adaptive response and 1 cGy-mediated G1 arrest. The above results indicate that induction of adaptive response by hsp25 and inducible hsp70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.