BCNU-Induced Sister Chromatid Exchanges Are Increased by X Irradiation

Abstract

The effect on sister chromatid exchange (SCE) induction in 9L rat brain tumor cells caused by combination treatment with BCNU [1,3-bis-(2-chloroethyl)-1-nitrosourea] and X-rays was studied. Over the dose and concentration ranges used in these experiments, BCNU induced relatively large numbers of SCE, while X-rays induced few SCE. When cells were X-irradiated immediately after BCNU treatment, the number of SCE induced was greater than the number of SCE expected by adding the number of SCE induced by each agent alone; the number of SCE induced as a result of this BCNU-X-ray interaction increased as the concentration of BCNU and/or dose of X-rays increased. When the addition of bromodeoxyuridine was delayed from 0-16 h after BCNU treatment, the number of SCE induced declined to control levels by 16 h. If X-irradiation was delayed for up to 16 h after BCNU treatment the same pattern of decrease was observed; the number of SCE induced at each time point was greater than that induced by BCNU and X-rays alone. X-irradiation from 0-16 h before BCNU treatment produced the same number of SCE as that produced by BCNU alone. The SCE assay is capable of detecting a drug-X-ray interaction in mammalian cells and provides a sensitive means of studying the sequencing and timing that leads to the interaction.