Enhancement of radiation-induced DNA-protein crosslinking by N-methylformamide.
The effects of the differentiating agent N-methylformamide (NMF) on radiation-induced DNA damage and repair in vitro were investigated using the alkaline elution assay. Two tumor cell lines were examined: Clone A, a human colon adenocarcinoma, and HCA-1, a murine hepatocarcinoma. Both cell lines showed changes suggestive of a better differentiated phenotype when exposed to NMF. Treatment with NMF enhanced the radiation sensitivity of Clone A cells but had no effect on the radiation response of HCA-1 cells. Irradiation of NMF-treated cells, both Clone A and HCA-1, induced the formation of DNA-protein crosslinks (DPCs). The level of DPCs induced increased linearly as a function of increasing gamma-ray dose. The DPCs did not seem to be the result of NMF exposure alone, but rather an NMF-mediated modification of the spectrum of gamma-ray-induced DNA lesions. When the DPCs were removed by proteolytic digestion, no NMF effect was observed on either strand-break formation or repair.
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005559:Formamides / Q000494:pharmacology*; D005720:Gamma Rays; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D011506:Proteins / Q000528:radiation effects*; D011836:Radiation Tolerance
D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D005559:Formamides; D011506:Proteins; D004247:DNA; D005978:Glutathione; C002950:methylformamide