Laboratory Medicine Research interests include mechanisms of chemical carcinogenesis, predictive assays for carcinogenic activity, risk assessments, and public cancer policy.
Chemical carcinogens can act through a variety of different modes of action.
Understanding the underlying mechanisms is critical in order to develop more accurate predictive assays and to formulate realistic cancer risk assessments. Our laboratory has developed whole animal DNA repair assays to assess genotoxic activity in cells in the liver, kidney, lung, trachea, skin, and spermatocytes. To provide a bridge between animal models and responses in humans, we have formulated parallel assays in human hepatocytes and bronchial epithelial cells. To address concerns with nongenotoxic carcinogens we have demonstrated the critical roles of organ-specific cytotoxicity, regenerative cell proliferation and altered gene expression. Research with chloroform has shown that tumor formation is secondary to initiation and promotional events associated with a state of chronic cytolethality and regenerative cell proliferation produced by daily bolus gavage dosing.