Transformation of BALB/c-3T3 Cells: Introduction

The data and results in this series ofpapers on chemical transformation of BALB/c-3T3 cells detail a substantial effort to understand the uses and limitations of this methodology in identifying chemicals with carcinogenic potential. This project is an important portion of an effort supported by the National Toxicology Program (NTP) to develop, evaluate, and validate various in vitro and in vivo methods that may be used to identify properties of chemicals that can predict carcinogenic activity or other toxicological effects. These efforts have the goals of improving our understanding of the nature of carcinogenic potential, understanding carcinogenic and toxicologic mechanisms, and identifying chemical properties that have predictive value and thereby reducing our dependence on the use of long-term rodent bioassays to define these end points. Among the methodologies that have been evaluated by the NTP are several assays that detect chemical-induced transformation in mammalian cells. Transformation assays assessed in this program used primary Syrian hamster embryo (SHE) cells, primary human fibroblasts, A31-1-13 clone of BALB/c-3T3 cells, and viral-vectored genes or viral-infected cells such as Simian adenovirus (SA7) infection of SHE or rat embryo fibroblasts infected with the Rauscher murine leukemia virus. These papers present several important conclusions regarding the BALB/c-3T3 transformation assay. There are some general conclusions that can be derived regarding mammalian cell transformation based on experience with these methodologies. Each method presents unique characteristics and positive and negative properties. It is important to emphasize that the context in which the activities and value of these systems has been judged. The literature results we have reported relate mostly to the ability of these transformation assays to identify carcinogens or noncarcinogens that have been recognized through long-term rodent bioassays conducted by the NTP and other toxicological effects derived from the same