A Bhas 42 cell transformation assay on 98 chemicals: the characteristics and performance for the prediction of chemical carcinogenicity

Abstract

The Bhas 42 cell transformation assay is a short-term system using a clone of the BALB/c 3T3 cells transfected with an oncogenic murine ras gene (v-Ha-ras). The assay has previously been reported to be capable of detecting the tumor-initiating and tumor-promoting activities of chemical carcinogens according to the different protocols, an initiation assay and a promotion assay, respectively. We applied this short-term assay to 98 chemicals to characterize the assay and evaluate its performance for the detection of chemical carcinogenicity. When the assay results were compared with the existing genotoxicity data, the Bhas 42 cell transformation assay could detect a considerable number of Ames-negative and Ames-discordant carcinogens: and the promotion assay detected most of those Ames-negative and -discordant carcinogens. This fact suggested that the Bhas 42 cells behaved as initiated cells in the transformation assay. The performance indices were calculated from the assay results of 52 carcinogens and 37 non-carcinogens. The concordance was 78%, sensitivity 73%, specificity 84%, positive predictivity 86%, negative predictivity 69%, false negative 27% and false positive 16%. Of these values, the concordance, specificity, negative predictivity and false positive were superior and the other performance indices were equivalent to those of conventional genotoxicity tests. From overall results, we concluded that the accuracy of prediction of chemical carcinogenicity would be improved by introducing the Bhas 42 cell transformation assay into the battery of in vitro assays.