[Modification of cellular radiosensitivity by NO-synthase inhibitors].
We recently reported that the treatment of V-79 and HeLa cells with nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) significantly reduced the level of the radiation-induced unstable chromosome aberrations. The stereoisomer D-NAME had no effect. We suggest that the radioprotective effect of L-NAME resulted from the action on the generation reactive radicals due to the inhibition of the NOS-activity. We tested this suggestion on the NO-resistant (ECV-304) and NO-sensitive (HeLa) cells, which were treated with L-NAME or aminoguanidine or D-NAME or cysteamine before gamma-irradiation. There are no significantly differences in radiosensitivity between these cells estimated after exposure by gamma-rays with different doses. However, the radioprotective effect of the NOS-inhibitors manifested only for HeLa. D-NAME had no radioprotective effect neither HeLa nor ECV-304. In contrast NOS-inhibitors, cysteamine treatment EVC-304 reduced the radiation-induced level chromosome aberrations almost twofold. The different mechanisms of the modification of cellular radiosensitivity are discussed.
Gil'iano
N Ia
NIa
Bondarev
G N
GN
Konevega
L V
LV
Semenova
E G
EG
Noskin
L A
LA
D002869:Chromosome Aberrations; D003543:Cysteamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005720:Gamma Rays; D006146:Guanidines / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006146:Guanidines; D011837:Radiation-Protective Agents; D009569:Nitric Oxide; D003543:Cysteamine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester