Enhanced radiation-induced fatal sensitivity and splenic lymphocyte apoptosis in mice with mutation in P/Q-type Ca2+ channel α1A subunit gene

Rolling mouse Nagoya (RMN) carries the mutation in a gene encoding for the α1A subunit of P/Q-type Ca2+ channel. This study was aimed to elucidate the role of the P/Q-type Ca2+ channel in radiosensitive and radioadaptive responses following whole-body X-irradiation by using RMN. Adult RMN and littermate controls (C3Hf/Nga) were subjected to a single exposure to X-irradiation at doses of 4 to 6.75 Gy. RMN were slightly more radiosensitive than controls: a decrease in the 25-day survival rates at 4 Gy and shortened survival time at 6.75 Gy. In both RMN and the controls, Bax- and TUNEL-positive lymphocytes increased in the white pulp of spleen 12 hours following X-irradiation at 3 Gy, and the inductions of Bax- and TUNEL-positive lymphocytes by the irradiation was apparently suppressed 2 weeks following pre-irradiation with a low dose (0.45 Gy). However, there were no differences in the frequencies of Bax- and TUNEL-positive lymphocytes between RMN and the controls in all irradiation groups. The results suggest that altered function of the P/Q-type Ca2+ channel may modify survival patterns of acutely irradiated, mutation-bearing RMN. Furthermore, radiosensitive and radioadaptive responses of Bax-mediated apoptosis of the splenic lymphocytes may not be altered in RMN. (author)