A derivative of vitamin B(3) applied several days after exposure reduces lethality of severely irradiated mice

Cheda, Aneta; Nowosielska, Ewa M.; Gebicki, Jerzy; Marcinek, Andrzej; Chlopicki, Stefan; Janiak, Marek K.

Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. In the present study we demonstrate for the first time that 1-methyl nicotinamide (MNA), a derivative of vitamin B(3), significantly (1.6 to 1.9 times) prolonged survival of BALB/c mice irradiated at LD(30/30) (6.5 Gy), LD(50/30) (7.0 Gy) or LD(80/30) (7.5 Gy) of γ-rays when the MNA administration started as late as 7 days post irradiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B(3) derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). These pro-survival effects did not seem to be mediated by stimulation of haematopoiesis, but might be related to anti-inflammatory and/or anti-thrombotic properties of the vitamin B(3) derivatives. Our results show that MNA may represent a prototype of a radioremedial agent capable of mitigating the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of ionizing radiation.