Original Articles

Relationship between radiation sensitization and DNA damage by bimolane

Yang-Pei Zhang, Yue-Neng Chen, Guo-Cai Fan, Shou-Xuan Xia

Abstract

It was reported that bimolane [AT1727; bis (N4-mopholino-methyl-3,5- dioxopiperazynyl)-l,2-ethane] could be used as a radiosensitizer in the treatment of radioresistant tumor. By means of Kohn’s alkaline elution method in combination with proteinase K digestion, the mechanism of action of bimolane on mouse S180-V tumor cells was elucidated. It was found that under 30 Gyγ-ray irradiation, the drug in a final concentration of 10-100μg/ml not only caused about 30% of cellular DNA to crosslink with protein, but also induced approximately equal amounts of DNA single strand breaks (SSB). Similar damaging effects had been observed in synchronized S phase S180-V cells, but in which the rejoining DNA SSB were found much slower than in non-synchronized cells. The effect on DNA is discussed in connection with the active imino-groups of the drug, which might be found in vivo after biotransformation.
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