This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Afshari, C. A. Articles by Barrett, J. C. Search for Related Content PubMed PubMed Citation Articles by Afshari, C. A. Articles by Barrett, J. C.

Induction of Neoplastic Progression in Syrian Hamster Embryo Cells Treated with Protein Phosphatase Inhibitors

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709 [C. A. A., S. K., H. M. B., T. B. W., J. C. B.]; Curriculum of Toxicology, University of North Carolina, Chapel Hill, North Carolina [C. A. A., J. C. B.]; and National Cancer Center Research Institute, Tokyo, Japan [H. F.]

In these studies, Syrian hamster embryo cells (SHE), which were isolated at different stages of neoplastic progression, were used to test the ability of the protein phosphatase inhibitors, okadaic acid and sodium orthovanadate (Na₃VO₄) to induce neoplastic progression. We observed that these chemicals can induce transition of the cells from one stage to the other at different points in the multistep process of neoplastic transformation. Three steps in this multistep process were studied: escape from cellular senescence, loss of a tumor suppressor gene function in immortal cells, and aquisition of anchorage-independent growth. Treatment of normal, primary SHE cells with okadaic acid or Na₃VO₄ allowed the cells to escape senescence and become immortal at a low frequency. The induction of immortality was associated with nonrandom chromosome changes, including trisomy 8 and 11 and monosomy 13 and Xq. The transition of preneoplastic cells to more advanced stages was also studied in immortal, nontumorigenic cells that either have retained (supB+) or have lost (supB-) the ability to suppress tumorigenicity of a transformed cell line in cell hybrids. SupB+ and supB- cells do not normally grow in agar, but supB- cells with grow in agar if additional growth factors are added. However, upon addition of protein phosphatase inhibitors, supB+ cells exhibited the supB- phenotype; for example, colony formation of supB+ cells was observed in agar supplemented with growth factors and protein phosphatase inhibitors. Following treatment, selection of these colonies showed that 89% of these cells heritably acquired the phenotype of cells that have lost the suppressor gene function (supB-). SupB- cells were also treated with protein phosphatase inhibitors in soft agar in the presence of additional growth factors. While the frequency of colonies in agar supplemented with growth factors in agar was not greatly enhanced, approximately 50% of the colonies acquired the ability to grow in agar autonomously without the supplemented growth factors, similar to tumorigenic cells. These studies suggest that Na₃VO₄ and okadaic acid induce progression of cells through various stages in this multistep system.

¹ Present address: Center for the Study of Aging and Human Development, Duke University Medical School, P. O. Box 3003, Durham, NC 27705.

² To whom requests for reprints should be addressed.

Received 10/ 6/92. Accepted 2/11/93.

This article has been cited by other articles:

				L. Le Hegarat, L. Puech, V. Fessard, J. M. Poul, and S. Dragacci Aneugenic potential of okadaic acid revealed by the micronucleus assay combined with the FISH technique in CHO-K1 cells Mutagenesis, May 1, 2003; 18(3): 293 - 298. [Abstract] [Full Text] [PDF]