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The Syrian Hamster Embryo (SHE) Cell Transformation Assay: Review of the Methods and Results
R.J. Mauthe
Pfizer Global Research and Development, Groton, CT 06340-8014
D.P. Gibson
The Procter and Gamble Company, Cincinnati, OH 45253-8707
R.T. Bunch
Pharmacia Corporation, Skokie, IL, 60077
L. Custer
Covance Laboratories, Vienna, VA 22182
The Syrian hamster embryo (SHE) cell-transformation assay represents a short-term in vitro assay capable of predicting rodent carcinogenicity of chemicals with a high degree of concordance (LeBoeuf et al [1996]. Mutat Res 356: 85—127). The SHE assay models the earliest identifiable stage in carcinogenicity, morphological cell transformation. In contrast to other short-term in vitro assays, both genotoxic and epigenetic carcinogens are detected. The SHE assay, originally developed by Berwald and Sachs (J Natl Cancer Inst 35: 641—661) and modifi ed as described by LeBoeuf and Kerckaert (Carcinogenesis 7: 1431—1440), was included in the International Life Sciences Institute, Health and Environmental Sciences Institute (ILSI/HESI). Alternative Carcinogenicity Testing (ACT) collaboration to provide additional information on the use of short-term in vitro tests in predicting carcinogenic potential. A total of 19 ILSI compounds have been tested in the SHE assay: 15 were tested for this project, whereas clofi brate, methapyrilene, reserpine, and Di(2-ethylhexyl ) phalate (DEHP) were tested previously. Of the 3 noncarcinogenic compounds tested, 2 were negative in the SHE assay, whereas ampicillin was tested positive. The remaining 16 compounds tested were either known rodent carcinogens and/or human carcinogens. From this group, 15 tested positive in the SHE assay whereas phenacetin, a genotoxic carcinogen, was tested negative. Therefore, overall concordance between the SHE assay and rodent bioassay was 89% (17/19), whereas concordance with known or predicted human carcinogens was 37% (7/19). Based on these data, it is concluded that the SHE cell-transformation assay has utility for predicting the results of the rodent carcinogenesis bioassay but lacks the selectivity to distinguish between rodent and human carcinogens.
Key Words: Epigenetic carcinogens • genotoxic carcinogen • in vitro assay • rodent carcinogenicity.
References
- LeBoeuf RA, Kerckaert GA, Aardema MJ, GibsonDP, Brauninger R., Isfort RJ (1996). The pH 6.7 Syrian hamster embryo cell transformation assay for assessing the carcinogenic potential of chemicals [review] [105 refs]. Mutat Res 356: 85—127.[Web of Science][Medline]
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- Berwald Y., Sachs L. (1965). In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. J Natl Cancer Inst 35: 641—661.[Web of Science][Medline]
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- LeBoeuf RA, Kerckaert GA (1986). The induction of transformed-like morphology and enhanced growth in Syrian hamster embryo cells grown at acidic pH. Carcinogenesis 7: 1431—1440.[Abstract/Free Full Text]
- Huberman E., Salzberg S., Sachs L. (1968). The in vitro induction of an increase in cell multiplication and cellular life span by the water soluble carcinogen dimethylnitrosamine. Proc Natl Acad Sci USA 59: 77—82.[Free Full Text]
- Isfort RJ, Kerckaert GA, LeBoeuf RA (1996). Comparison of the standard and reduced pH Syrian hamster embryo (SHE) cell in vitro transformation assays in predicting the carcinogenic potential of chemicals [review] [262 refs]. Mutat Res 356: 11—63.[Web of Science][Medline]
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- Kerckaert GA, Isfort RJ, Carr GJ, Aardema MJ, LeBoeuf RA (1996). A comprehensive protocol for conducting the Syrian hamster embryo cell transformation assay at pH 6.70. Mutat Res 356: 65—84.[Web of Science][Medline]
[Order article via Infotrieve]
- Pienta RJ, Poiley JA, Lebherz WB (1977). Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. Int J Cancer 19: 642—655.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- LeBoeuf RA, Kerchaert GA (1987). Enhanced morphological transformation of early passage Syrian hamster embryo cells cultured in medium with a reduced bicarbonate concentration and pH. Carcinogenesis 8: 689—697.[Abstract/Free Full Text]
- LeBoeuf RA, Kerckaert GA, Aardema MJ, Poiley JA, Raineri R. (1990). Enhanced morphological and neoplastic transformation of Syrian hamster embryo cells cultured at pH 6.70. Prog Clin Biol Res 340D: 219—228.
- Custer L., Gibson DP, Aardema MJ, LeBoeuf RA (2000). A refi ned protocol for conducting the low pH 6.7 Syrian hamster embryo (SHE) cell transformation assay. Mutat Res 455: 129—139.[Web of Science][Medline]
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- Armitage P. (1971). Statistical Methods in Medical Research. Blackwell Scientifi c Publications, Oxford, pp 135—138.
Toxicologic Pathology, Vol. 29, No. 1 suppl,
138-146 (2001)
DOI: 10.1080/019262301753178546
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