The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.
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 modified 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 clofibrate, 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.
Mauthe
R J
RJ
Pfizer Global Research and Development, Groton, CT 06340-8014, USA.
Gibson
D P
DP
Bunch
R T
RT
Custer
L
L
D000826:Animal Testing Alternatives; D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008647:Mesocricetus; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D011237:Predictive Value of Tests; D051381:Rats; D015203:Reproducibility of Results
D002273:Carcinogens; D009153:Mutagens