In Vitro Assays for the Prediction of Tumorigenic Potential of Non-genotoxic Carcinogens

Abstract

As screening methods to predict carcinogenicity, genotoxicity assays have a major issue in that many carcinogens are negative in such assays. Non-genotoxic mechanisms, which are at least initially independent of direct DNA damage, can play a causal role in carcinogenesis. Also, it is predicted that among these non-genotoxic carcinogens, many will be tumor promoters. There is therefore a need to develop tumor promoter assays, and in vitro assays have been developed to detect phenomena such as the inhibition of gap junctional intercellular communication, the promotion or inhibition of cell differentiation, the expression of Epstein-Barr virus early antigen (EBV-EA), and cell transformation assays. However, none of these assays has been adopted in the battery of official safety screening tests for chemicals. One reason is that some methods are not simple for routine screening. Given this lack, we established a novel short-term in vitro method to detect the tumor promoting potential of chemicals, the Bhas promotion assay. This is a cell transformation assay using Bhas 42 cells. It has many advantages compared with other focus formation (cell transformation) assays. Transferability and applicability of this assay was confirmed by an inter-laboratory collaborative study. Furthermore, our study has demonstrated that the Bhas promotion assay has practical utility value in monitoring the promoting potential of environmental contaminants.