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Dexamethasone Effects on Induction of Neoplastic Transformation by Fujinami Sarcoma Virus in an in Vitro Chick Embryo Periosteal Model for Osteosarcoma¹

Connective Tissue Research Group [C. B., H. C. T.] and Division of Molecular and Developmental Biology [T. P.], Mount Sinai Hospital Research Institute, Toronto, Ontario M5G 1X5, and Faculty of Dentistry, University of Toronto, [H. C. T. and C. A. G. M.], Toronto, Ontario M5G 1G6, Canada

Recently we have developed a model in vitro system for the study of factors regulating the histogenesis of osteosarcoma. In this system, Fujinami sarcoma virus (FSV) induces osteosarcomatous changes such as increased cell proliferation and altered patterns of bone and non-mineralized matrix (osteoid) formation. Such changes can be quantitated at the individual cell level, by computer-assisted morphometry. Here we report on the effects of dexamethasone (DEX) on FSV-induced neoplastic transformation and osteogenesis in chick embryonic periosteum cultures, as reflected by a series of histopathological parameters. Most significantly, it was found that compared to 10^-9 M DEX treated cultures, in 10^-7 M DEX pretreated cultures, the bone/osteoid ratio was increased due to a relative increase in the area of bone and a decrease in the area of osteoid. The number of [³H]thymidine-labeled cells decreased significantly, while the proportion of alkaline phosphatase positive cells increased. Double-label immunohistochemistry (with anti-P140^gag-fps) and histochemistry for alkaline phosphatase activity was performed, to demonstrate production of the oncogene-encoded protein, and osteoblastic differentiation, respectively. In an in vitro transformation assay single cells derived from 10^-9 M DEX treated cultures formed a significantly higher number of colonies than those obtained from 10^-7 M DEX pretreated cultures. Taken together, the data indicate that in the chick embryonic periosteum culture system, pretreatment with 10^-7 M DEX inhibits the ability of FSV to induce neoplastic transformation. This effect is probably the result of DEX-induced cell differentiation, prior to infection with FSV.

¹ Supported by grants from the Medical Research Council of Canada.

² To whom requests for reprints should be addressed, at Connective Tissue Research Group, Mount Sinai Hospital Research Institute, Room 975, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

Received 5/ 2/88. Revised 8/18/88. Accepted 9/16/88.