The Way Forward

The four in vitro methods (cell transformation assays and a GJIC assay) available for validation will serve only as partial replacements for use in a tiered testing scheme or test battery (Maurici, et al., 2005, p. 180). A battery of in vitro genotoxicity, cell transformation, and GJIC assays can be used to identify the carcinogenic potential of a substance, but there are limitations to the existing in vitro methods. They generally lack metabolic capacity and are not developed using cells relevant to the target organ. Nongenotoxic carcinogens act via a variety of mechanisms and are therefore difficult to predict. Even when in vitro assays are used to identify a possible carcinogen, an animal bioassay is required to confirm the prediction and determine the potency and target organ.

The ECVAM Task Force on Carcinogenicity concluded that the multiple stages and complex biology of carcinogenesis cannot be adequately modeled by in vitro/in silico approaches at this time and that a full replacement battery will not be available within the next 10 years. Considering the lack of a plan for full replacement of the animal bioassays at this time, several groups have provided recommendations for reductions and refinement (Maurici, et al., 2005, pp 178-179; MacDonald, et al., 2004).

For more on The Way Forward, read the following invited commentaries on carcinogenicity/genotoxicity:

• Use of Genetic Toxicology Testing for Predicting Carcinogenicity: A Multi-Stakeholder Approach by Marilyn Aardema
• Use of In Silico Evaluation of Chemical Genotoxicity by Makoto Hayashi
• Genotoxicity and Carcinogenicity: Which Alternative Strategy(ies)? by Gladys D. Ouédraogo
• Animal Use in Genetic Toxicity Tests for Identifying Potential Carcinogens by Errol Zeiger