DNA damage induced in cultured human alveolar (L-132) cells by exposure to dimethylarsinic acid.
Gene damage in cultured human alveolar (L-132) cells induced by exposure to dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics in mammals, was studied. DNA single-strand breaks and DNA-protein cross-links were induced by the treatment of L-132 cells with 10 mM DMAA. These kinds of damage appeared at 8 hr after start of exposure to DMAA. As regards DNA-protein cross-links, the DNA was found to bind not only to core histone proteins but also linker histone (H1) and nonhistone proteins. Furthermore, the cross-links were formed by the binding to serine or threonine residues of H1 or nonhistone proteins through phosphate moieties of the DNA. The induction of the alkali-labile sites in DNA in DMAA-treated L-132 cells was observed prior to that of DNA single-strand breaks and DNA-protein cross-links. As one of the alkali-labile sites in DNA, we estimated apurinic/apyrimidinic (AP) sites in DNA. The present study suggests that the DNA single-strand breaks and DNA-protein cross-links induced by the treatment of L-132 cells with DMAA occurred via the formation of AP sites in the DNA and that the DNA-protein cross-links were produced by a Schiff-base reaction between amino groups of nuclear proteins and aldehyde groups of AP sites in the DNA and the DNA single-strand breaks, by a beta-elimination reaction on AP sites in the DNA.
Department of Biochemical Toxicology, Nihon University College of Pharmacy, Chiba, Japan.
K
K
Kato
H
H
Hayashi
A
A
Hasegawa
K
K
Yamanaka
S
S
Okada
D002101:Cacodylic Acid / Q000633:toxicity*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000633:toxicity; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000187:drug effects; D006801:Humans; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D002101:Cacodylic Acid