Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate |
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Authors: | Rani AShobha; Qu Da-Qin; Sidhu Maninder K; Panagakos Fotinos; Shah Varsha; Klein Kenneth M; Brown Nicholas; Pathak Sen; Kumar Suriender |
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Institution: | Departments of Biochemistry & Molecular Biology Newark, NJ
1Pathology, UMDNJ-New Jersey Medical School Newark, NJ
2Department of Cell Biology, The University of Texas, M.D. Anderson Cancer Center Houston, TX, USA |
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Abstract: | Epidemiological studies have indirectly linked compounds ofchromium, nickel and arsenic to human carcinogenesis. However,there is no evidence that metal compounds can transform humancells to the tumorigenic phenotype in culture. We show herethat exposure to 36 µM NiS04 for 4896 h resultsin transformation of an immortal, non-tumorigenic, osteoblast-likecell line, HOS TE85, to the tumorigenic phenotype. Continuouspassaging following treatment leads to the formation of a fewdense foci. The cells isolated and expanded from the foci aremorphologically transformed, and form anchorage-independentcolonies of the size and abundance comparable to that formedby Kirsten murine sarcoma virus transformed HOS TE85 cells.The transformed cells from tumors in nude mice, have enhancedlevels of plasminogen activators and have lost the ability toform model bone matrix on extended culture in the presence ofascorbic acid and ß-glycerophosphate. A number ofcell lines have been established from nude mouse tumors. Cytogeneticanalysis reveals 16 marker chromosomes and an aberrant chromosome16. This is the first report of the transformation of a humancell line to tumorigenic phenotype by a metal carcinogen. |
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