Comparison of the standard and reduced pH Syrian Hamster Embryo (SHE) cell in vitro transformation assays in predicting the carcinogenic potential of chemicals

Abstract

A comprehensive review of the Syrian Hamster Embryo (SHE) cell transformation literature was performed in order to catalogue the chemical/physical entities which have been evaluated for in vitro cell transformation potential. Both reduced pH (pH 6.7) and standard pH (pH 7.1–7.3) SHE cell testing protocols were considered. Based upon this analysis, over 472 individual chemical/physical agents and 182 combinations of chemical/physical agents have been tested under the standard pH conditions, while over 56 chemical/physical agents have been tested under reduced pH conditions. Of the 472 chemical/physical agents tested at the standard pH, 213 had in vivo carcinogenicity data available. Of these 213 chemical/physical agents, 177 were carcinogens while 36 were non-carcinogens. The results of testing the SHE transformability of these 213 chemical/physical agents indicates that the standard pH SHE cell transformation assay had a concordance of 80% ( 171 213 ), a sensitivity of 82% ( 146 177 ), and a specificity of 69% ( 25 36 ). Of these 213 chemical/physical agents, 53% ( 112 213 ) were tested more than once often in more than one laboratory, with a 82% ( 92 112 ) interlaboratory agreement rate, thus providing confirmatory results. Carcinogenicity data were available for 48 of the 56 chemical/physical agents tested for SHE cell transformation under the reduced pH conditions. The SHE cell transformation assay under reduced pH conditions had a concordance of 85% ( 41 48 ), a sensitivity of 87% ( 26 30 ), and a specificity of 83% ( 15 18 ). For Salmonella-negative carcinogens, the standard pH SHE assay correctly predicted carcinogenicity 75% ( 48 64 ) of the time while the reduced pH SHE assay correctly predicted carcinogenicity for Salmonella-negative carcinogens 78% ( 14 18 ) of the time. For chemical/physical agents tested under both the reduced pH and standard pH conditions, the standard pH and reduced pH SHE cell assays had a 69% ( 22 32 ) agreement rate. Under the reduced pH conditions, the SHE assay correctly predicted rodent carcinogenicity in 86% ( 25 29 ) of the chemicals tested under both reduced and standard pH conditions. Under standard pH conditions, the SHE assay correctly predicted rodent carcinogenicity in 69% ( 20 29 ) of the chemicals tested under both reduced and standard pH conditions. Collectively, these data indicate that the SHE cell transformation assay is predictive for rodent carcinogenicity under either reduced or standard pH conditions. Importantly, the assay displays better performance and appears to have improved carcinogen prediction capability under reduced pH conditions.