On the Reaction Kinetics of the Radioadaptive Response in Cultured Mouse Cells

Abstract

The reaction kinetics of radioadaptive response of low doses of X-rays have been studied in quiescent cultured mouse cells. Mouse m5S cells pre-exposed in G₁ to low doses of X-rays became insensitive to the induction of chromosome aberrations, mutation toward 6-thioguanine resistance, and cell killing. Adapted cells were, however, more susceptible to morphological transformation by subsequent high challenging doses of X-rays. The cytogenetic adaptation, which lasted about 20 h pertained to a narrow dose range. X-ray doses below and above 0·1 Gy appeared to be recognized as different signals; higher doses of X-rays were incapable of inducing adaptation and rapidly extinguished the adapted condition. Treatment with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and hydrogen peroxide, but not the xanthine/xanthine oxidase superoxide-generating system, mimicked X-rays in inducing adaptation when applied at low doses. Over-exposure to TPA or inhibitors of protein kinase C (PKC) abrogated the adaptive response to X-rays, providing evidence for the involvement of a PKC-mediated signalling pathway. The lack of radioadaptive response in a tumorigenic variant, clone 6110, and its restoration in the morphological revertant obtained by introducing human chromosome 11 further suggested that interference of signalling pathways may alter radioadaptive responses in malignant cells.