High frequencies of chromatid aberrations produced during G 2 in human lymphocytes by very low doses (0.025–0.4 Gy) of X-rays in combination with inhibitors of DNA synthesis

Abstract

Whole-blood cultures of human lymphocytes were exposed in the G 2-phase (3.5 h before harvesting) to various doses of X-rays and post-treated for 3 h with inhibitors of DNA synthesis. The inhibitors used were 2′-deoxyadenosine (dAdo), hydroxyurea (HU) and 1-ß- d-arabinofuranosylcytosine (ara-C). To prevent deamination of dAdo by adenosine deaminase (ADA), the dAdo treatments were carried out in the presence of the ADA inhibitor coformycin. HU and Ara-C were used either alone or in combination. After the 3-h inhibitor treatments, the cultures were harvested and slides prepared and analyzed for chromatid aberrations in metaphase. When the inhibitors were used at concentrations high enough to cause marked chromosome damage by themselves, very low doses of X-rays (0.025–0.2 Gy) were sufficient to produce a dramatic increase in the frequency of chromatid aberrations. High frequencies of chromatid aberrations were also obtained when cultures that had received moderate doses of X-rays (0.4–0.8 Gy) were post-treated with low inhibitor concentrations that produce no or only a few aberrations by themselves.