Neoplastic transformation of human small airway epithelial cells induced by arsenic.
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.
Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA. gw2154@columbia.edu
Gengyun
G
Wen
Gloria M
GM
Calaf
Michael A
MA
Partridge
Carlos
C
Echiburú-Chau
Yongliang
Y
Zhao
Sarah
S
Huang
Yunfei
Y
Chai
Bingyan
B
Li
Burong
B
Hu
Tom K
TK
Hei
D018053:Arsenites / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D017670:Sodium Compounds / Q000633:toxicity*; D019098:Telomerase; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D018053:Arsenites; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; C017947:sodium arsenite; C509186:TERT protein, human; D019098:Telomerase; D016283:Proto-Oncogene Proteins p21(ras)