DNA repair and chromosome aberrations: The effect of cytosine arabinoside on the frequency of chromosome aberrations induced by radiation and chemicals

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Abstract
The frequency of x‐ray‐induced chromosome aberrations in G0 human lymphocytes was greatly increased when cells were incubated with cytosine arabinoside (ara‐C) after irradiation. The frequency of dicentrics increased with increasing ara‐C incubation times (one, two, and three hours). Lymphocytes from Down syndrome individuals were more sensitive to aberration induction by x‐rays in G0, and the increase in dicentric frequency with ara‐C incubation was much more rapid than with normal cells. When G2 normal lymphocytes were x‐irradiated and incubated for two or three hours with ara‐C until fixation, there was a large increase in deletion frequency compared to cells x‐irradiated and incubated in the absence of ara‐C. However, no exchanges were observed in the presence of ara‐C, compared to 0.29 per cell as when x‐rays alone were given. These results form the basis for a discussion of the mechanism of aberration induction by x‐rays.Experiments with two chemicals, 4‐nitroquinoline‐N‐oxide and methyl methanesulfonate, show that chromosome‐type aberrations can be induced in G1 treated lymphocytes incubated with ara‐C. However, these chemicals, in the absence of ara‐C incubation, induced no aberrations in G1 at the concentrations used. The mechanism of aberration induction is discussed, particularly in terms of whether or not chemicals can be defined as S‐phase dependent.

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