Increased sensitivity of mammalian cell cultures to radiomimetic alkylating agents following incorporation of 5-bromodeoxyuridine into cellular DNA

Cultures in vitro of a murine mast cell tumor were incubated with 5-bromodeoxyuridine in order to incorporate 5-bromouracil into cellular DNA. Cells containing 5-bromouracil in their DNA exhibited an increased sensitivity to two biological alkylating agents, mechlorethamine (nitrogen mustard, HN2) and dimethylmyleran. This increase in sensitivity, however, was lower than the corresponding increase in radiosensitivity. Sensitivity to increased incubation temperatures was not significantly changed by the pretreatment of cultures with 5-bromodeoxyuridine. It is concluded that DNA represents the primary target for the action of these alkylating agents on cell reproduction. The results obtained suggest, however, that the chemical alterations of DNA caused by mechlorethamine, dimethylmyleran and X-rays may be different.