G2 repair and the formation of chromosomal aberrations II. The effect of hydroxyurea, 5-fluorodeoxyuridine and caffeine on streptonigrin- and 8-ethoxycaffeine-induced chromosome damage in Vicia faba

Abstract

The effects of hydroxyurea (HU) and 5-fluorodeoxyuridine (FdUrd) on streptonigrin (SN)- and 8-ethoxycaffeine (EOC)-induced chromosome damage were studied in root tips of Vicia faba. In addition, SN- and EOC-treated roots were post-treated with caffeine, alone or in combination with HU. The HU and FdUrd post-treatments were given the last few hours before fixation and the caffeine post-treatments immediately after the exposure to SN or EOC. Both HU and FdUrd strongly increased the frequency of SN-induced gaps, chromatid breaks and isochromatid breaks of the NU-type, and the enhancement was particularly striking in cells that had been exposed to SN while in early interphase. Potentiation by HU was obtained in cells that were exposed to the inhibitor 1 1/2 to 5 hr before they reached metaphase. The potentiating effect of FdUrd on SN-induced chromosome damage was completely reversed by thymidine. It was concluded that aberrations induced by SN were formed in late G 2 from lesions, the repair of which required DNA synthesis. Post-treatments with caffeine strongly enhanced the frequency of all types of aberrations induced by SN in early interphase. The observation that HU was equally effective in enhancing SN-induced chromosome damage in combination with caffeine as when given alone suggests that post-treatments with caffeine increase the frequency of HU-sensitive lesions to the same extent as they increase the frequency of chromosomal aberrations. Neither HU nor caffeine had any effect on the frequency of aberrations induced by EOC, an observation which suggests that EOC-induced aberrations are formed by a mechanism different from that responsible for the formation of SN-induced aberrations.