Abstract
Radiation induced DNA double strand breaks are believed to be important lesions involved in processes related to cell killing, induction of chromosome aberrations and carcinogenesis. This paper reports the effects of the radioprotector 2-[(aminopropyl)amino]ethanethiol (WR-1065) on radiation-induced DNA damage and repair in V79 cells using the neutral elution method performed at pH 7.2 or pH 9.6. WR-1065 (4 mM) was added to the culture medium either 30 minutes prior to and during irradiation with Cobalt-60 gamma rays (for dose response experiments) or during the repair times tested (for DNA rejoining experiments). The results indicate that WR-1065 is an effective protector against the formation of radiation-induced double-strand breaks in DNA as measured using a neutral elution technique at either pH. The protector reduced the strand scission factors by 1.44 and 1.77 in experiments run at pH 9.6 and pH 7.2, respectively. The kinetics of DNA double-strand rejoining were dependent upon the pH at which the neutral elution procedure was performed. Unlike the results obtained with alkaline elution, rejoining of DNA breaks was unaffected by the presence of WR-1065 at either pH.
Highlights
Considerable interest has recently been expressed in the use of phosphorylthioate drugs as adjuvants to radiotherapy (Kligerman et al, 1980, 1984; Takahasi et al, 1986)
The effect of the radiation protector WR- 1065 (4mM) on Double-strand breaks (DSB) formation was measured by using the neutral elution technique at pH 9.6 and pH 7.2
DSB formation was reduced when the protector was present at the time of irradiation
Summary
Considerable interest has recently been expressed in the use of phosphorylthioate drugs as adjuvants to radiotherapy (Kligerman et al, 1980, 1984; Takahasi et al, 1986). This interest is based upon an early observation by Yuhas and Storer, (1969) that WR-2721 differentially protects normal as compared to tumour cells. Utley et al, (1976) using wholebody autoradiography with labelled WR-2721, later demonstrated that little or no uptake of the protector was observed in an EMT/6 tumour, wide distribution was noted in surrounding normal tissues
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