Effects of inhibitors of DNA synthesis on spontaneous and ultraviolet light-induced sister-chromatid exchanges in Chinese hamster cells

Abstract

Effects of inhibitors of DNA synthesis on spontaneous and ultraviolet light (UV)-induced sister-chromatid exchanges (SCE) were examined in a Chinese hamster cell line, V79 B-1. The inhibitors used were hydroxyurea (HU), 1-beta-D-arabinofuranosylcytosine (ara-C), aphidicolin (APC), 2',3'-dideoxythymidine triphosphate (ddTTP), neocarzinostatin (NCS), novobiocin (NB) and cycloheximide (CHX). HU, ara-C, and APC increased spontaneous SCE frequency, and had a synergistic effect on UV-induced SCE frequency. DdTTP, NCS and NB failed to show any statistically significant effect on either spontaneous or UV-induced SCE frequencies, though NCS and NB did slightly increase both spontaneous and UV-induced SCE frequencies. On the contrary, CHX decreased spontaneous SCE frequency, and more drastically, also UV-induced SCE frequency. These results are interpreted with respect to the replicating fork of DNA, a structure postulated to be involved in the formation of spontaneous and UV-induced SCE. A new model for SCE formation is proposed.