Cell transformation assays as predictors of human carcinogenicity - The report and recommendations of ECVAM Workshop 39

This is the report of the thirty-ninth of a series of workshops organised b y the European Centre for the Validation of Alternative Methods (ECVAM). EC VAM's main goal, as defined in 1993 by its Scientific Advisory Committee, i s to promote the scientific and regulatory acceptance of alternative method s which are of importance to the biosciences and which reduce, refine or re place the use of laboratory animals. One of the first priorities set by ECV AM was the implementation of procedures which would enable it to become wel l-informed about the state-of-the-art of non-animal test development and va lidation, and the potential for the possible incorporation of alternative t ests into regulatory procedures. It was decided that this would be best ach ieved by the organisation of ECVAM workshops on specific topics, at which s mall groups of invited experts would review the current status of in vitro tests and their potential uses, and make recommendations about the best way s forward (1). In addition, other topics relevant to the Three Rs (reductio n, refinement and replacement) concept of alternatives to animal experiment s have been considered in several ECVAM workshops. The workshop on Cell Transformation Assays as Predictors of Human Carcinoge nicity was held in Angera, Italy on 12-16 October 1998. The principal aim o f the workshop was to seek consensus on ways of increasing the use of mamma lian cell transformation assays, especially in human cell systems, for fund amental and applied studies in carcinogenesis, and for the regulatory testi ng of carcinogens, and to make practical recommendations to facilitate this process. This was endorsed by the fundamental belief of all the participan ts that the further development, evaluation, routine use and eventual regul atory acceptance of cell transformation assays, in conjunction with other t oxicity information, would improve the overall process of safety and risk a ssessment of carcinogenicity, for the protection of human health. This beli ef was based on the fundamental premise that the process of in vitro cell t ransformation closely models the carcinogenic process in vivo. It should be noted that this report is focused on three rodent cell transfo rmation systems, i.e. those employing primary Syrian hamster embryo cells ( SHE cell assay), and two systems based on the mouse fibroblast cell lines, Balb/c 3T3 and C3H/10T1/2. This report also covers the recent advances with human cell transformation systems.