Comparative evaluation of three mammalian cell transformation assay systems

Abstract

One cellular transformation assay system (Syrian hamster embryo (SHE) primary cells) and two viral mediated transformation systems (primary Syrian hamster embryo cells infected with Simian adenovirus type 7 (SHE/SA7), and a rat fibroblast cell line (2FR450) infected with Rauscher leukemia virus (Rat/RLV] were evaluated using a group of nine "model" and five coded chemicals. The purpose of the project was to establish the intra- and interlaboratory reproducibility of the assays and to provide a basis for objective comparisons between the systems. This is a preliminary evaluation of the assay systems using the results for these chemicals tested in eight collaborating laboratories under the auspices of the National Toxicology Program (NTP). The endpoint measured in each system is very different and a positive response in each had to be separately defined. The assay systems all produced a response to carcinogens and in most instances the responses could be qualitatively reproduced in the different laboratories. However, the assays differed significantly in their ability to demonstrate dose-related effects. In addition, multiple tests or modified assay procedures were required with every system in order to insure that chemicals had been adequately tested. In each system, technical or procedural limitations exist that preclude the application of these assays to routine chemical testing at this time. Among these limitations were ambiguity in scoring morphological transformation, significant but poorly defined influence of reagents such as serum or metabolic activation systems on test performance, and difficulty in repeating responses to a given chemical. Additional efforts to overcome these limitations will be necessary in order to make these test systems of use in routine testing of unknown chemicals for genetic toxicity.