DNA repair and chromosome aberrations: the effect of cytosine arabinoside on the frequency of chromosome aberrations induced by radiation and chemicals.
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.
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000528:radiation effects; D003561:Cytarabine / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000648:ultrastructure; D008741:Methyl Methanesulfonate / Q000633:toxicity; D013997:Time Factors; D014965:X-Rays
D003561:Cytarabine; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate