Cell culture model systems are key to our basic understanding of many biochemical and molecular biological processes, and have revealed many important mechanisms in chemical carcinogenesis. However, the use of cell culture models as tools in risk assessment have been underutilized because of uncertainties surrounding correlating cell culture effects with similar events in a whole organism.

Medaka brain cells in culture

To begin to address this issue the Wise Laboratory in collaboration with the Winn Laboratory are investigating how mutagenesis is induced by metals. The work builds on a guppy-sized transgenic fish (Medaka) that the Winn laboratory developed to help assess health hazards in the environment. This fish carries a gene that serves as a mutation reporter gene, which quantifies and identifies the types of mutations that occur after the fish is exposed to a chemical. This Medaka fish model is ideal for studying waterborne contaminants such as metals, and is valued as a comparative model for human carcinogenesis.

The Wise laboratory is developing cell lines from different organs and sexes of the Medaka model, which will also carry the same mutation reporter gene. These cells lines when treated with a metal will also produce data that will indicate the types and probable location of mutations caused by that chemical. By comparing the results of the two models, the work will yield important new information on how cell culture and whole animal models relate with respect to level of exposure to a chemical, types of mutations that occur and their mechanism of formation.

This research is important because it will enhance the utility of the existing data that scientists have already obtained from cell culture models and will likely help reduce our reliance on whole animal models. If successful, this research will dramatically help risk assessors and risk managers better determine the risk of exposure to metals for humans.

Medaka fin cells in culture

Medaka gill cells in culture

Relevant Wise Laboratory Publications

Goodale, B.C., Walter, R., Pelsue, S.R., Thompson, W.D., Wise, S.S., Winn, R.N., Mitani, H. and Wise, J.P. Sr. The cytotoxicity and genotoxicity of hexavalent chromium in medaka (Oryzias latipes) cells. Aquatic Toxicology, in press.