Involvement of preferential formation of apurinic/apyrimidinic sites in dimethylarsenic-induced DNA strand breaks and DNA-protein crosslinks in cultured alveolar epithelial cells.
We previously found that lung-specific DNA damage induced by administration of dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, in mice might be due to dimethylarsenic peroxyl radical [(CH3)2AsOO.] produced in the further metabolic processing of DMAA. Further analysis of DNA damage was performed in the present study using a human embryonic cell line of alveolar epithelial (L-132) cells. Alkali-labile sites in DNA were produced prior to DNA single-strand breaks (SSB) and DNA-protein crosslinks (PC) in L-132 cells by exposure to 10mM DMAA. An experiment using methoxyamine (MA), an agent reacting with the aldehyde group of apurinic/apyrimidinic (AP) sites in DNA, indicated that, of the alkali-labile sites formed by exposure to DMAA, major ones were AP sites. These findings suggest that SSB and PC induced by exposure of L-132 cells to DMAA occurred via the formation of AP sites in DNA. That is, SSB were produced by a beta-elimination reaction on AP sites in the DNA and PC by a Schiff-base reaction between amino groups of nuclear proteins and aldehyde groups of AP sites.
Department of Biochemical Toxicology, Nihon University College of Pharmacy, Chiba, Japan.
K
K
Yamanaka
H
H
Hayashi
K
K
Kato
A
A
Hasegawa
S
S
Okada
D002101:Cacodylic Acid / Q000494:pharmacology*; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology; D007700:Kinetics; D010545:Peroxides; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism
D004277:DNA, Single-Stranded; D005609:Free Radicals; D006898:Hydroxylamines; D010545:Peroxides; C049375:perhydroxyl radical; D004247:DNA; C005214:methoxyamine; D002101:Cacodylic Acid