title: DNA single-strand breaks in L-132 cells resulting from inhibition of repair polymerization shortly after exposure to dimethylarsinic acid.
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 alpha, delta and epsilon, and the latter inhibits DNA polymerase beta. Generally, DNA polymerases delta and epsilon are thought to be associated with necleotide excision (long patch) repair and polymerase beta 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 micrograms/ml aph plus 10 mM hydroxyurea (HU) for the last 1 h of the DMAA exposure. Also, when DNA polymerase beta was inhibited with 10 mM ddT plus 1 microM 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 delta and/or epsilon, and polymerase beta, functioned independently on different lesions induced after exposure to DMAA.
authors.affiliation: Nihon University College of Pharmacy, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamanaka
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: N
authors.initials: N
authors.lastname: Oku
authors.forename: S
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D001704:Biopolymers; D002101:Cacodylic Acid / Q000494:pharmacology*; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000187:drug effects*; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans
chemical_list: D001704:Biopolymers; D004277:DNA, Single-Stranded; D006540:Herbicides; D002101:Cacodylic Acid