Abstract
DNA single-strand breaks due to the inhibition of repair polymerization in cultured human pulmonary epithelial (L-132) cells after exposure to dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, were examined. The strand breaks were detected by an alkaline elution method with the use of inhibitors of DNA polymerase, aphidicolin (aph) and 2', 3'-dideoxythymidine (ddT); the former inhibits DNA polymerases α, δ and ε, and the latter inhibits DNA polymerase β. Generally, DNA polymerases δ and ε are thought to be associated with necleotide excision (long patch) repair and polymerase β with base excision (short patch) repair. After exposure of the L-132 cells to 10 mM DMAA, the breaks occurred in a time-dependent manner during incubation for 1-6 h under the inhibition of aph-sensitive polymerases with 50 μg/ml aph plus 10 mM hydroxyurea (HU) for the last 1 h of the DMAA exposure. Also, when DNA polymerase β was inhibited with 10 mM ddT plus 1 μM methotrexate (MTX), the exposure of L-132 cells to 10 mM DMAA for 6 h significantly induced DNA single-strand breaks. An experiment of the co-treatment with both aph and ddT suggested that in the DNA repair process, aph-sensitive polymerases, probably polymerases δ and/or ε, and polymerase β, functioned independently on different lesions induced after exposure to DMAA.
