The relationship between DNA and chromosome damage after bleomycin treatment: dose-response measurements

The molecular basis for chromosome aberration formation has been studied using the sensitive techniques of premature chromosome condensation and DNA alkaline elution. The dose response of Chinese hamster ovary cells to bleomycin treatment at the DNA and chromosome levels was compared. Each DNA elution curve showed a 2-component profile, with a more sensitive component apparent at low doses. The chromosome aberration curves also exhibited a 2-component profile when determined in G2-PCC; however, this phenomenon was less apparent when chromosome damage was enumerated in mitotic figures. These results suggest that differential sensitivity to bleomycin exists within the cellular chromatin. The effect of dose rate on aberration formation was examined by administering bleomycin at 2 concentrations that, with different treatment times, yielded equivalent amounts of DNA damage. The chromatid exchange rate was independent of dose rate, suggesting that rapidly repaired DNA lesions are not involved in the formation of exchanges.