Study on the repair of the radioinduced lesions involved in the formation of chromosomal aberrations in G0 human lymphocytes after exposure to γ-rays and fast neutrons

Cytosine arabinoside (ara-C), an inhibitor of DNA synthesis and repair, has been used to study the mechanisms of formation of chromosomal aberrations after exposure to low- and high-LET radiation. When G0 human lymphocytes were exposed either to γ-rays or to d(50 MeV)-Be neutrons and immediately treated with ara-C for increasing periods of time, the frequency of aberrations (dicentrics) increased sharply. For γ-rays, the enhancement increased with the duration of the treatment up to 5 h, whereas for neutrons, an ara-C treatment lasting for 5 h was no more effective than treatment for 3 h. These results were confirmed by the second experiment in which ara-C was administered for 3 h with an increasing time delay following irradiation. Since no increase in the dicentric frequency was observed when ara-C was administered 5 h after γ-irradiation, it is suggested that the induced breaks rejoined within that time. For neutrons, the data were conflicting since the repair was completed within 3 h after a dose of 0.5 Gy, and in approximately 5 h after a dose of 2.0 Gy. From both experiments, it appears that γ-rays and fast neutrons produce similar types of lesions, as ara-C increased the frequencies of aberrations induced by both types of radiation. However, the ara-C treatment resulted in a smaller increase in aberrations following neutron irradiation. According to the enzymatic nature of break formation and the mode of action of ara-C on the polymerase activity, it is suggested that, in addition to double-strand breaks, single-strand breaks could be the lesions involved in the repair processes inhibited by ara-C. Single-strand breaks formed directly or by secondary reactions would, therefore, be one of the major lesions responsible for the aberrations produced by γ and neutron radiations.