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Nitric oxide-mediated Bcl-2 stabilization potentiates malignant transformation of human lung epithelial cells.

Authors
Azad-N; Iyer-AKV; Wang-LY; Lu-YJ; Medan-D; Castranova-V; Rojanasakul-Y
Source
Am J Respir Cell Mol Biol 2010 May; 42(5):578-585
NIOSHTIC No.
20037368
Abstract
Hexavalent chromium (Cr(VI)) compounds are known human carcinogens associated with the incidence of lung cancer. Although a direct correlation between Cr(VI) exposure and lung cancer has been established, several studies aimed at generating animal models for Cr(VI) have yielded inconsistent data that do not affirmatively support findings from epidemiologic studies. Because the lack of a good animal model has hindered the identification of molecular mechanisms involved in Cr(VI) exposure, we developed an in vitro model that facilitates mechanistic studies of Cr(VI)-induced carcinogenesis. We report here that long-term exposure to Cr(VI) leads to the malignant transformation of nontumorigenic human lung epithelial cells. Cr(VI)-transformed cells exhibited loss of contact inhibition, colony formation, and increased rates of cell invasion, migration, and proliferation, as compared with passage-matched control cells. Cr(VI)-transformed cells evaded apoptosis by a mechanism involving S-nitrosylation and stabilization of Bcl-2 protein in a nitric oxide dependent manner. This study establishes an important in vitro model that facilitates mechanistic studies of Cr(VI)-induced carcinogenesis, and elucidates a novel mechanism that causes apoptosis-resistant malignant transformation of nontumorigenic lung cells in response to a human carcinogen.
Keywords
Aerosol-particles; Airborne-particles; Air-contamination; Biological-effects; Biological-function; Carcinogenicity; Cell-alteration; Cell-biology; Cell-damage; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Cellular-reactions; Chemical-hypersensitivity; Chemical-properties; Chemical-reactions; Environmental-hazards; Exposure-assessment; Exposure-levels; Exposure-methods; Immunochemistry; Inhalants; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lead-compounds; Lung-cancer; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Mathematical-models; Molecular-structure; Physiological-effects; Physiological-response; Physiological-testing; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis; Author Keywords: nitric oxide; Bcl-2; malignant transformation; hexavalent chromium; apoptosis
CODEN
AJRBEL
CAS No.
18540-29-9
Publication Date
20100501
Document Type
Journal Article
Email Address
neelam.azad@hamptonu.edu
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
1044-1549
NIOSH Division
HELD
Source Name
American Journal of Respiratory Cell and Molecular Biology
State
WV; VA
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