Validation of an in vitro screening test for predicting the tumor promoting potential of chemicals based on gene expression.

Chemical carcinogenesis is a multifactorial process comprising two main stages: initiation and promotion. Tumor promoters cause the development of tumors in initiated cells and the majority of them are non-genotoxic carcinogens. The identification of tumor promoters is important for preventing cancer. We previously identified 22 specific gene markers using a global gene expression analysis of chemically induced tumor promotion and established an in vitro real-time PCR screening assay for the assessment of the tumor promoting potential of chemicals in BALB/c 3T3 cells. Our in vitro tumor promoter screening test, based on these marker genes, enables earlier assessment, and is easier to conduct than classical methods. The general applicability of these markers, however, was unknown. In this study, to evaluate the performance of a set of markers, we independently validated a separate sample set, which had various structures and properties. Independent validation of the signature of 63 test chemicals showed an accuracy, sensitivity, and specificity of the assay of 96.8%, 97.0% and 96.7%, respectively. These results indicate that the tumor promoting activity assay, based on the expression of 22 marker genes, will become a valuable tool for rapid screening of potential tumor promoters. Copyright (c) 2009 Elsevier Ltd. All rights reserved.