Induction of morphological transformation, anchorage-independent growth and plasminogen activators in non-tumorigenic human osteosarcoma cells by lead chromate.
The possible carcinogenicity of insoluble chromium (VI) compound, PbCrO4, in human cells has been tested using a nontumorigenic human osteosarcoma cell line (HOS, TE 85). Electron microscopic studies show that PbCrO4 is phagocytosed by HOS cells and accumulates within the vacuoles in the cytoplasm. A number of cell lines have been isolated following multiple treatment of HOS cells with PbCrO4. These cell lines are morphologically different from HOS cells, form anchorage-independent colonies in soft agar and form quickly regressing small tumor nodules in athymic nude mice. The cellular and secreted plasminogen activator (PA) levels of 5 cell lines isolated after PbCrO4 treatment are increased up to 8 fold and up to 10 fold respectively as compared to untreated HOS controls. SDS-PAGE analysis in the presence of copolymerized substrates is consistent with increase in 55 kDa urokinase-type PA (u-PA) and 68 kDa tissue-type PA (t-PA). These results show that PbCrO4 treatment leads to stable phenotypic changes indicative of the transformation of HOS cells.
Sidhu
M K
MK
Department of Biochemistry and Molecular Biology, UMD-New Jersey Medical School, Newark 07103.
Fernandez
C
C
Khan
M Y
MY
Kumar
S
S
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002840:Chromates / Q000633:toxicity*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010960:Plasminogen Activators / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D002840:Chromates; D007854:Lead; C031895:lead chromate; D010960:Plasminogen Activators