title: 3,4-Dimethoxyphenyl bis-benzimidazole derivative, mitigates radiation-induced DNA damage.
abstract: Radiation-induced DNA damage initiates a series of overlapping responses that include DNA damage recognition and repair, induction of cell cycle checkpoints, senescence and/or apoptosis. This study assessed the DNA damage response and whole genome expression profile in two mammalian cell lines (HEK and U87) in response to (5-{4-methylpiperazin-1-yl}-2-[2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl] benzimidazole) DMA and ionizing radiation. DMA has been shown to act as a potent radiation protector, yielding significant levels of protection, i.e., 20.9% in HEK cells and 21.2% in U87 cells. Our findings revealed treatment with DMA significantly reduced γ-H2AX, 53BP1 and Rad51 foci formation after irradiation. MAP kinase, WNT signaling and p53 pathways were found to be activated in DMA-treated cells. In addition, the DNA damage response genes, HSP70, HSPD1, PRDX1, PRX, CALR, NPM, UBC, and SET showed differential regulation in DMA, DMA + radiation and radiation-treated cells. The data suggest that DMA-influenced repertoire of repair proteins, which are an indispensable part of the cell, interplay with each other to reduce DNA damage and maintain the genomic integrity of the cell.
authors: Department of Chemistry, University of Delhi, Delhi, India. vibhadelhi6@gmail.com
authors: Atul
authors: A
authors: Ranjan
authors: Navrinder
authors: N
authors: Kaur
authors: Vinod
authors: V
authors: Tiwari
authors: Yogendra
authors: Y
authors: Singh
authors: Madan Mohan
authors: MM
authors: Chaturvedi
authors: Vibha
authors: V
authors: Tandon
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D011837:Radiation-Protective Agents / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D016166:Free Radical Scavengers; C468783:H2AX protein, human; D006657:Histones; D011837:Radiation-Protective Agents; C031000:benzimidazole