An explanation of interspecific differences in sensitivity to X-ray-induced chromosome aberrations and a consideration of dose-response curves.

Using 1-beta-D-arabinofuranosylcytosine (AraC) which is an inhibitor of DNA-repair resynthesis, previous studies have shown that the frequency of chromosome-type aberrations is influenced by the rate of repair of araC-inhibitable DNA damage. The experiments described here are a further test of this hypothesis and also an attempt to determine if the different sensitivities of lymphocytes of different species to X-ray-induced aberrations are related to the rate of endonucleolytic incision during repair of DNA damage. Unstimulated lymphocytes from 4 species were exposed to an X-ray dose of 200 rad, and then incubated with araC for 0, 1, 2, 3 or 4 h. The aberration frequencies increased in all species up to 3-4 h. It was also clear that the rate of increase was different between species and was approximately proportional to the ratios of X-ray-induced aberrations observed in the absence of araC. For example, human lymphocytes are approximately twice as sensitive as rabbit lymphocytes to the induction of aberrations by X-rays and the rate of increase of aberrations in the presence of araC was about twice as great in human as rabbit lymphocytes. In addition, using 50, 100, 200 or 300 rad of X-rays and treating human lymphocytes for 0, 1, 2 or 3 h in araC post-irradiation, we have shown that the rate of increase in aberrations is proportional to the amount of araC-inhibitable DNA damage; with a limiting dose at about 50 rad. These results appear to provide a basis for interpreting differences in sensitivities to aberration induction among mammalian species.