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Critical Reviews™ in Oncogenesis

Published 4 issues per year

ISSN Print: 0893-9675

ISSN Online: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

Indexed in

The Syrian Hamster Embryo (SHE) Cell Transformation System: A Biologically Relevant In Vitro Model− with Carcinogen Predicting Capabilities− of In Vivo Multistage Neoplastic Transformation

Volume 6, Issue 3-6, 1995, pp. 251-260
DOI: 10.1615/CritRevOncog.v6.i3-6.30
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ABSTRACT

Neoplastic transformation is a multistep process that can be modeled in vitro using Syrian hamster embryo (SHE) cells.SHE cell multistage transformation involves several intermediate stages, including morphological transformation, immortality, acquisition of tumorigenicity, and malignant progression. Analysis of the molecular alterations that occur at each stage indicates that morphological transformation results from both carcinogen-induced irreversible chromosomal/genetic mutations and reversible genetic events, including altered DNA methylation. Morphological transformation results from a block in the cellular differentiation of progenitor and determined stem-like cells in the SHE cell population via alteration in the expression of the H19 tumor suppressor gene and other genes. Immortality results from genetic mutations in growth factor responsiveness, including loss of growth suppression by TGFβ and autocrine growth factor production, and genomic stability, resulting in genomic instability and an increased mutation rate. Acquisition of tumorigenicity involves loss of tumor suppressor gene function, altered mitogenic signal transduction, mutation of oncogenes, acquisition of anchorage independent growth, and chromosomal aberrations. Malignant progression is associated with alterations in extracellular matrix growth characteristics, alterations in cytoskeleton structure, elevated fibrinolytic activity, secretion of proteases, and changes in extracellular matrix protein secretion. Together, these changes model the alterations observed during in vivo neoplastic transformation and possibly explain why the SHE assay, as a carcinogen screening tool, is able to identify carcinogens with a 80 to 85% accuracy.

CITED BY
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  5. Ahmadzai Abdullah A., Trevisan Júlio, Pang Weiyi, Riding Matthew J., Strong Rebecca J., Llabjani Valon, Pant Kamala, Carmichael Paul L., Scott Andrew D., Martin Francis L., Classification of agents using Syrian hamster embryo (SHE) cell transformation assay (CTA) with ATR-FTIR spectroscopy and multivariate analysis, Mutagenesis, 30, 5, 2015. Crossref

  6. Ahmadzai A. A., Trevisan J., Pang W., Patel I. I., Fullwood N. J., Bruce S. W., Pant K., Carmichael P. L., Scott A. D., Martin F. L., Classification of test agent-specific effects in the Syrian hamster embryo assay (pH 6.7) using infrared spectroscopy with computational analysis, Mutagenesis, 27, 3, 2012. Crossref

  7. Ahmadzai A. A., Trevisan J., Fullwood N. J., Carmichael P. L., Scott A. D., Martin F. L., The Syrian hamster embryo (SHE) assay (pH 6.7): mechanisms of cell transformation and application of vibrational spectroscopy to objectively score endpoint alterations, Mutagenesis, 27, 3, 2012. Crossref

  8. Zhang H, Borman H.D, Myhr B.C, Enhancement of the morphological transformation of Syrian hamster embryo (SHE) cells by reducing incubation time of the target cells, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 548, 1-2, 2004. Crossref

  9. Nang Choy Wai, Genotoxic and Nongenotoxic Mechanisms of Carcinogenesis, in Genetic Toxicology and Cancer Risk Assessment, 2001. Crossref

  10. Keshava Nagalakshmi, Zhou Gu, Spruill Michelle, Ensell Mang, Ong Tong-man, Carcinogenic potential and genomic instability of beryllium sulphate in BALB/c-3T3 cells, in Molecular Mechanisms of Metal Toxicity and Carcinogenesis, 2001. Crossref

  11. Dragan Yvonne P., Pitot Henry C., The Effects of Triphenylethylene Antiestrogens on Parameters of Multistage Hepatocarcinogenesis in the Rat, in Hormone Therapy in Breast and Prostate Cancer, 2009. Crossref

  12. Combes Robert, Balls Michael, Curren Rodger, Fischbach Michel, Fusenig Norbert, Kirkland David, Lasne Claude, Landolph Joseph, LeBoeuf Robert, Marquardt Hans, McCormick Justin, Müller Lutz, Rivedal Edgar, Sabbioni Enrico, Tanaka Noriho, Vasseur Paule, Yamasaki Hiroshi, Cell Transformation Assays as Predictors of Human Carcinogenicity, Alternatives to Laboratory Animals, 27, 5, 1999. Crossref

  13. Kameda Hideto, Risinger John I., Han Bing-Bing, Baek Seung Joon, Barrett J. Carl, Abe Tohru, Takeuchi Tsutomu, Glasgow Wayne C., Eling Thomas E., Expression of Gab1 Lacking the Pleckstrin Homology Domain Is Associated with Neoplastic Progression, Molecular and Cellular Biology, 21, 20, 2001. Crossref

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