Transformation of immortal, non-tumorigenic 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 evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and 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 have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen.
Department of Biochemistry & Molecular Biology, UMDNJ-New Jersey Medical School, Newark.
A S
AS
Rani
D Q
DQ
Qu
M K
MK
Sidhu
F
F
Panagakos
V
V
Shah
K M
KM
Klein
N
N
Brown
S
S
Pathak
S
S
Kumar
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002871:Chromosome Banding; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007621:Karyotyping; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009532:Nickel / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D008769:Methylnitronitrosoguanidine; C029938:nickel sulfate; D009532:Nickel