Author(s): Wise SS, Elmore LW, Holt SE, Little JE, Antonucci PG, , Wise SS, Elmore LW, Holt SE, Little JE, Antonucci PG,
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Abstract Hexavalent chromium (Cr(VI)) is a metal of increasing public health concern, as exposure to it is widespread and it is a well-established cause of human bronchial carcinomas and fibrosarcomas. The water-insoluble Cr(VI) salts are potent carcinogens compared to the water soluble salts; yet the genotoxic mechanisms of both may be mediated by soluble Cr(VI) ions. Currently, these mechanisms are poorly understood. Emerging evidence suggests that initial cell culture models used to study the general toxicity of Cr(VI) may be suboptimal for investigating mechanisms specific to human bronchial cells. Accordingly, we have developed a new model system of human bronchial cells by introducing hTERT, the catalytic subunit of human telomerase, into primary human bronchial fibroblasts (PHBF). We have isolated a stable, clonally derived cell line, WHTBF-6, that demonstrate reconstitution of telomerase activity and maintenance of telomere lengths with increasing culture age. WHTBF-6 has been characterized as having an extended in vitro lifespan, a normal growth rate, a normal diploid karyotype that is maintained over time, and exhibits serum-dependent contact-inhibited anchorage-dependent growth. Moreover, we find that both particulate and soluble hexavalent chromium induce a pattern and degree of cytotoxicity and clastogenicity in WHTBF-6 that is similar to the parental PHBF cells. Because telomerase does not compromise growth or the response to Cr(VI), our results indicate that this is an excellent system for studying the mechanisms of Cr(VI) and potentially other carcinogens implicated in the development of lung cancer.
This article was published in Mol Cell Biochem
and referenced in Journal of Environmental & Analytical Toxicology