Effects of arsenic on DNA damage and repair in human fetal lung fibroblasts.

Previous studies suggest that arsenic may be both mutagenic and co-mutagenic. In this report, we examined the effects of sodium arsenite (As) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on unscheduled DNA synthesis (UDS) in human fetal lung fibroblasts (2BS cells) by 3H/14C double-labeling and liquid-scintillation counting techniques. Arsenic at concentrations of 1, 5 and 10 microM increased UDS value, indicating that arsenic directly damaged DNA and did not inhibit DNA repair. In addition, UDS induced by 34 microM MNNG in combination with arsenic was significantly increased by 3 microM As and not affected by 0.1, 0.5, 1.0 and 5 microM As, also indicating that arsenic did not inhibit the excision and polymerization steps of DNA repair. Based on the results and a previous study that 3 microM As is more efficient than 1 and 5 microM As in the induction of DNA-protein crosslinks, we proposed that arsenic may enhance the mutagenicity of other compounds by inducing DNA-protein crosslinks rather than inhibiting DNA repair.