Particulate arsenic trioxide induces higher DNA damage and reactive oxygen species than soluble arsenite in lung epithelial cells

Abstract

Environmental arsenic exposure is associated with lung cancer. Arsenic is the first substance known to cause lung cancer by two distinct routes, ingestion and inhalation, in the forms of soluble arsenite and particulate arsenic trioxide, respectively. In comparison to significant progresses in research on mechanisms for lung carcinogenesis of arsenic ingestion, inhalation arsenic exposure route in particulate form and its lung carcinogenic mechanisms are relatively under-investigated. Fundamentally, it remains unclear whether particulate arsenic exposure is in a dissolved form and whether particulate exposure yields higher damage. Utilizing dynamic laser scattering, particulate arsenic trioxide exposure in cellular system was confirmed to be in particulate form instead of dissolved form. Using immunofluorescence, particulate arsenic trioxide was demonstrated to generate dramatically higher oxidative DNA damage and strand break, as well as significantly higher superoxide, in lung epithelial cell lines such as BEAS-2B, HSAEC1-KT, and SAE, comparing to soluble arsenite exposure at similar or lower concentration. This study demonstrated that particulate arsenic trioxide exposure yields higher damage in lung epithelial cells, and indicated that inhalation route of particulate arsenic exposure plays an important role in lung carcinogenesis.