Abstract
Stable nitroxide radicals such as TEMPO and carbamoyl-PROXY (CM-PROXYL) are reportedly good radiation protectors and we demonstrated in the previous meeting that methoxycarbonyl-PROXYL (MC-PROXYL) is also a good radiation protector. In the present study, we prepared another 4-substituted PROXYL, hydroxymethyl-PROXYL (HM-PROXYL) and compared these three PROXYLs with respect to radiation protection, prevention of DNA damage, and distribution in mice.
The PROXYLs had different in vivo radiation protection activity assessed as a 30 day-survival of mice (C3H, male) after X-ray irradiation.; HM-PROXYL > MC-PROXYL ≈ CM-PROXYL. On the other hand, their protection in cellular level examined as the recovery of colony formation inhibited by X-ray irradiation was similar among them: HM-PROXYL ≈ MC-PROXYL ≈ CM-PROXYL. Further, in vitro radiation protection against DNA damage measured by cleavage of plasmid DNA (pBR322) or formation of 8-OHdG in salmon DNA caused by X-ray irradiation was also similar among them. Oxidation potential of CM-, MC-, and HM-PROXYL are 0.662, 0.677 and 0.589 V, respectively, and reduction potential of them are -0.688, -0.687 and -0.686 V, respectively, showing only little difference. The concentration in the blood and bone marrow showed the order of HM-PROXYL > MC-PROXYL ≈ CM-PROXYL. Therefore, the difference of in vivo radioprotection of these PROXYLs could be mainly explained by the difference in the distribution of these compounds in the body.
