Colcemid inhibits the rejoining of the nucleotide excision repair of UVC-induced DNA damages in Chinese hamster ovary cells

• Published in: Mutation research Vol. 588; no. 2; pp. 118 - 128
• Main Authors: Li, Hsun, Chang, Tai-Wei, Tsai, Yi-Chi, Chu, Shu-Fu, Wu, Yi-Yin, Tzang, Bor-Show, Liao, Chu-Bin, Liu, Yin-Chang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.12.2005; Elsevier
• Subjects: Animals; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; CHO Cells; Cisplatin - pharmacology; Colcemid; Cricetinae; Cricetulus; Demecolcine - toxicity; DNA - drug effects; DNA - radiation effects; DNA Damage - drug effects; DNA Repair - drug effects; DNA Replication - drug effects; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Medical sciences; Mitosis - drug effects; Nucleotide excision repair; Toxicology; Ultraviolet Rays; UVC-induced DNA damages; UVC-induced DNA damages; Nucleotide excision repair; Colcemid; Toxicology; Excision; DNA; Nucleotide; Genetics; Lesion; Repair; CHO cell line
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/j.mrgentox.2005.09.005

In our previous study, we found that colcemid, an inhibitor of mitotic spindle, promotes UVC-induced apoptosis in Chinese hamster ovary cells (CHO.K1). In this study, a brief treatment of colcemid on cells after but not before UV irradiation could synergistically reduce the cell viability. Although colcemid did not affect the excision of UV-induced DNA damages such as [6–4] photoproducts or cyclobutane pyrimidine dimers, colcemid accumulated the DNA breaks when it was added to cells following UV-irradiation. This colcemid effect required nucleotide excision repair (NER) since the same accumulation of DNA breaks was barely or not detected in two NER defective strains of CHO cells, UV5 or UV24. Furthermore, the colcemid effect was not due to semi-conservative DNA replication or mitosis since the colcemid-caused accumulation of DNA breaks was also seen in non-replicating cells. Moreover, colcemid inhibited rejoining of DNA breaks accumulated by hydroxyurea/cytosine arabinoside following UV irradiation. Nevertheless, colcemid did not affect the unscheduled DNA synthesis as assayed by the incorporation of bromodeoxyuridine. Taken together, our results suggest that colcemid might inhibit the step of ligation of NER pathways.