Mechanism of fiber carcinogenesis: from reactive radical species to silencing of the beta igH3 gene.
Although the U.S. Environmental Protection Agency has restricted the industrial use of regulated forms of asbestos in the United States since the early 1970s, environmental exposure to asbestos remains a health concern in the United States and is a significant health issue among developing countries. Exposure to asbestos is associated with chronic pulmonary diseases and cancer of the lung, pleura, and peritoneum. The mechanism of fiber carcinogenesis is far from clear and is likely to be complex, depending on fiber dimensions, surface properties, and physical durability. The induction of reactive oxygen and nitrogen species upon phagocytosis of fibers plays an important role in fiber genotoxicity. The beta igH3, a secreted protein induced by the transforming growth factor-beta and essential for cell adhesion, is downregulated in asbestos-induced tumorigenic human bronchial epithelial cells. Ectopic expression of the beta igH3 gene abrogates the tumorigenic phenotype and suggests that the gene plays a causal role in fiber carcinogenesis. A better understanding of the carcinogenic mechanism of asbestos and other mineral fibers will provide useful information on interventional and preventive measures for asbestos-mediated diseases such as human pleural and peritoneal mesotheliomas.
Hei
Tom K
TK
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. tkh1@columbia.edu
Xu
An
A
Huang
Sarah X
SX
Zhao
Yongliang
Y
D001194:Asbestos / Q000009:adverse effects*; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D004781:Environmental Exposure / Q000009:adverse effects; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019016:Mineral Fibers / Q000009:adverse effects; D009153:Mutagens / Q000009:adverse effects*; D012140:Respiratory Tract Diseases / Q000235:genetics* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D000099222:betaIG-H3 Protein
D001194:Asbestos; D002274:Carcinogens, Environmental; D016326:Extracellular Matrix Proteins; D019016:Mineral Fibers; D009153:Mutagens; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein