TRANSFORMATION OF IMMORTAL, NONTUMORIGENIC OSTEOBLAST-LIKE HUMAN OSTEOSARCOMA CELLS TO THE TUMORIGENIC PHENOTYPE BY NICKEL SULFATE

Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evide nce that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 muM NiSO4 for 4 8-% h results in transformation of an immortal, non-tumorigenic, osteo blast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuo us passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphological ly transformed, and form anchorage-independent colonies of the size an d abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta-glycerophosphate. A number of cell lines ha ve been established from nude mouse tumors. Cytogenetic analysis revea ls 16 marker chromosomes and an aberrant chromosome 16. This is the fi rst report of the transformation of a human cell line to tumorigenic p henotype by a metal carcinogen.