title: Cleavage enhancement of specific chemical bonds in DNA by cisplatin radiosensitization.
abstract: X-ray photoelectron spectroscopy (XPS) is harnessed as an in situ efficient characterization technique for monitoring chemical bond transformation in DNA and cisplatin-DNA complexes under synergic X-ray irradiation. By analyzing the variation of relative peak area of core elements of DNA as a function of irradiation time, we find that the most vulnerable scission sites in DNA are those containing phosphate and glycosidic bonds. Compared to DNA, the effective rate constants of the corresponding phosphodiester and glycosidic bond cleavages for cisplatin-DNA complexes are 1.8 and 1.9 folds larger. These damages and their enhancements are similar to those induced by low energy electrons (LEE). Consistently, the magnitude of the secondary electron distribution produced by the X-rays on the cisplatin-DNA complexes is considerably increased compared to that of pristine DNA. The data suggest that DNA radiosensization by cisplatin results not only from the sensitization of DNA to the action of LEE, but also from an increase the production of LEE at the site of binding of the cisplatin. The results provide new insights into the mechanisms of cisplatin-induced sensitization of DNA under X-ray irradiation, which could be helpful in the design of new cisplatin-based antitumor drugs.
authors.affiliation: Fujian Provincial Key Laboratory of Photocatalysis, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, People's Republic of China.
authors.forename: Fangxing
authors.initials: F
authors.lastname: Xiao
authors.forename: Xinglan
authors.initials: X
authors.lastname: Luo
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects* / Q000528:radiation effects; D004583:Electrons; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D004247:DNA; C427203:calf thymus DNA; D002945:Cisplatin