Environmental Health Perspectives 105, Supplement 5, September 1997: Article by Hei et al.

Environmental Health Perspectives 105, Supplement 5, September 1997

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Malignant Transformation of Immortalized Human Bronchial Epithelial Cells by Asbestos Fibers

Tom K. Hei, Li J. Wu, and Chang Q. Piao

Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York

Abstract
Although asbestos is a well-established lung carcinogen, there currently is no suitable human cell model in which to examine the underlying cellular and molecular changes associated with fiber-mediated bronchial carcinogenesis. Using a recently established transformation model based on a human papillomavirus-immortalized human bronchial epithelial cell line, we successfully transformed these BEP2D cells after a single, 7-day treatment with a 20-µg/ml (4 µg per cm ² area) dose of Union Internationale Contre le Cancer (UICC) Rhodesian chrysotile fibers. Asbestos treatment resulted in a surviving fraction of 0.18 compared to control cells. Transformed cells developed through a series of sequential steps, including altered growth kinetics, resistance to serum-induced terminal differentiation, and anchorage-independent growth, before becoming tumorigenic to form progressively growing tumors in nude mice. Seven tumorigenic cell lines were isolated and determined to be of human epithelial origin based on immunofluorescent staining of keratin and isozyme analysis. Analysis of tumor DNA revealed no mutations at either codon 12 or 13 in any the ras oncogenes. An independent role for K-ras mutation in fiber carcinogenesis, therefore, cannot be confirmed. This model provides a unique opportunity to study the cellular and molecular changes at the various stages in fiber-mediated neoplastic transformation of human bronchial epithelial cells. -- Environ Health Perspect 105(Suppl 5):1085-1088 (1997)

Key words: asbestos, bronchial epithelial cells, fibers, chrysotile, bronchial carcinogenesis, immunofluorescent staining

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 1 July 1997.
This work was supported in part by grants ES05786 and ES06831 from the National Institute of Environmental Health Sciences.
Address correspondence to Dr. T.K. Hei, Center for Radiological Research, Vanderbilt Clinic 11-218, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032. Telephone: (212) 305-8462. Fax: (212) 305-3229. E-mail: tkh1@Columbia.edu
Abbreviations used: PCR, polymerase chain reaction; TPA,12-O-tetradecanoylphorbol acetate; UICC, Union Internationale Contre le Cancer.

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Last Update: October 28, 1997