Study of supra-additive effect by chemical agent association and X-ray irradiation on the DNA damage in base level

Igarashi, Shosuke; Onuki, Toshihiko; Sakamoto, Fuminori  

We have found specific base positions in the DNA cleavage by the irradiation of X-rays after association of a cisplatin with DNA. In cancer therapy it is well known that application of X-rays radiation with cisplatin dosage enhances the anti-cancer effect. However, the mechanism of enhancement in the anti-cancer has not been elucidated in the level of DNA base. We have developed a new approach for the determination of the DNA cleavage position using the Sanger method. Here we have specified the positions of base cleaved by X-ray radiation with cisplatin association with DNA. The cleavage patterns of the DNA irradiated by X-ray show that the DNA was cleaved by 100 Gy irradiation, and the four kinds of bases were cleaved. Ciplatin associated DNA without the irradiation was not cleaved. On the other hand, the ciplatin associated DNA specifically enhanced the cleavage at the bases of "guanine" and "adenine". When the irradiation increased to 150 Gy, the specific cleavage at the "guanine" and "adenine" were still detected. These results indicate that supra-additive effect by cisplatin association and X-ray irradiation on the DNA damage was caused by the specific cleavage at the base positions of "guanine" and "adenine".