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 H-3/C-14 double-labeling and liquid-scintillation counting techniques. Arsenic at concentrations of 1, 5 and 10 mu M increased UDS value, indicating that arsenic directly damaged DNA and did not inhibit DNA repair. In addition, UDS induced by 34 mu M MNNG in combination with arsenic was significantly increased by 3 mu M As and not affected by 0.1, 0.5, 1.0 and 5 mu M 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 mu M AS is more efficient than 1 and 5 mu M 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.