Differential effect of 9 beta-chloro-16, 16-dimethyl prostaglandin E2 (nocloprost) on the radiation response of human normal fibroblasts and colon adenocarcinoma cells.
The possible influence of 9 beta-chloro-16,16-dimethyl prostaglandin E2 (nocloprost) on the effect of 137Cs gamma irradiation was investigated comparatively in human normal fibroblasts and colon adenocarcinoma cells. By itself, the compound did not influence the proliferation of cells of either cell type or the clonogenic capacity of carcinoma cells. Moreover, nocloprost did not induce any DNA strand breakage, as evaluated by neutral elution, in cells of either cell type. A 2-h incubation with nocloprost before irradiation induced an enhancement of fibroblast survival after an exposure of 10 Gy. This protective effect was not observed in adenocarcinoma cells under the same treatment conditions. The amount of double-strand breaks induced by 50 Gy was reduced in normal cells but not in tumor cells exposed to the prostaglandin analog before irradiation. Moreover, incubation with nocloprost for 2 h after irradiation remarkably enhanced the rate of rejoining of DNA breaks in fibroblasts but not in adenocarcinoma cells. Overall, these findings indicate a specific radioprotective effect of nocloprost in normal cells and no influence of the compound on the cytotoxic effect of ionizing radiation on colon adenocarcinoma cells.
Zaffaroni
N
N
Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Villa
R
R
Orlandi
L
L
De Pascale
A
A
Del Mastro
S
S
Silvestrini
R
R
D000230:Adenocarcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011461:Prostaglandins F, Synthetic; C048895:nocloprost