The effect of cytosine arabinoside on the frequency of X-ray-induced chromosome aberrations in normal human leukocytes.

The yield of X-ray-induced chromosome aberrations in unstimulated human lymphocytes is greatly enhanced when the cells are incubated with cytosine arabinoside (ara-C) after irradiation. There is an increase in aberration yield with increasing time of incubation in ara-C (1, 2 or 3 h). When G2 cells are X-irradiated and incubated with ara-C until fixation, the deletion yields are considerably increased, but no interchanges are observed. In the absence of ara-C, 0.29 interchanges per cell were observed. The G2 results suggest that ara-C inhibits the repair of damage that leads to the formation of exchange aberrations. The increase in yield in unstimulated lymphocytes is interpreted to be due to an accumulation of strand breaks caused by ara-C inhibition of repair; when the inhibition is reversed with deoxycytidine, these breaks can interact to form aberrations. A possible mechanism for the induction of chromosome aberrations by X-rays is offered on the basis of these results.