Gene damage induced in human alveolar type II (L-132) cells by exposure to dimethylarsinic acid.
To analyze the mechanisms of arsenic-induced gene damage, found previously in lungs of mice and rats orally administered dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, we employed an in vitro system using human alveolar type II (L-132) cells. The exposure to 10 mM DMAA for 10 hr caused significant single-strand breaks in DNA of the cells. At an earlier period of the exposure, the replicative DNA synthesis was markedly suppressed, and the chain length of the nascent DNA was shorter than that of the control, suggesting that the template DNA received some modification other than strand breaks. The modification, being repairable, was sensitive to ultraviolet irradiation to cause strand breaks. These results suggest the possibility of DNA-adduct formation at the early period of DMAA exposure in L-132 cells.
Tezuka
M
M
University of Shizuoka School of Pharmaceutical Sciences, Japan.
Hanioka
K
K
Yamanaka
K
K
Okada
S
S
D002101:Cacodylic Acid / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis
D012313:RNA; D004247:DNA; D002101:Cacodylic Acid