Abstract
Human small airway epithelial cells (SAECs) previously immortalized with human telomerase reverse transcriptase (h-TERT) were continuously treated with sodium arsenite at a dose of 0.5 microg/mL in culture for up to 6 months. Arsenic-treated cells progressively displayed an increase in transformed phenotype including enhanced growth saturation density, plating efficiency, and anchorage-independent growth and invasion capability compared with their nontreated control cells. To determine whether arsenic-induced cell transformation was associated with genomic instability, treated and control cells were also analyzed for micronuclei formation. A 4.8-fold increase in micronuclei incidence in arsenic-treated cells was detected in conjunction with increased N-phosphonacetyl-l-aspartate (PALA)-resistant characteristics. In addition, arsenic-treated cells showed an increase in c-H-ras, c-myc, and c-fos protein expression relative to controls. The change in oncoprotein expression correlated with a decrease in wild-type p53 expression and hyperphosphorylated retinoblastoma. Taken together, these results strongly suggest that h-TERT immortalized human small airway epithelial cells underwent step-wise transformation after inorganic arsenic treatment.
Highlights
Arsenic is a trace element found naturally in the environment
The former arsenical species are metabolized by methylation to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in vivo, which are carcinogenic
The human telomerase reverse transcriptase (h-TERT) immortalized SAEC cells grew as a contact-inhibited monolayer with a population doubling time of ~24 h
Summary
Arsenic is a trace element found naturally in the environment. Inorganic arsenic has been recognized as a human carcinogen for more than a hundred years [2], scientists have been unable to elucidate its carcinogenetic mechanisms. Arsenic is a naturally occurring metalloid, and humans are exposed through contaminated soil, food, and water [3]. Occupational exposure occurs mainly through inhalation of airborne particles derived from semiconductor and glass manufacturing or power generation by the burning of arsenic-contaminated coal [2,4,5]. Arsenic can be classified into two types, inorganic and organic [6]. The former arsenical species are metabolized by methylation to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in vivo, which are carcinogenic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
