In Vitro System for Studying Metabolism of Environmental Chemicals in Human Cells
Annual rept. 30 Apr 1992-29 Apr 1993
SRI INTERNATIONAL MENLO PARK CA
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The objective of the project is to establish and use an in vitro system of intact hepatocytes from rodent and human liver to develop quantitative data on the metabolism of toxic chemicals that can be used in risk assessments. Currently, two different in vitro models are most frequently used for comparative metabolism studies-isolated hepatocytes and precision-cut liver slices. In the second year of the project, hepatocytes and liver slices from rat and human liver Were compared to determine their capability to metabolize chloroform and a model substrate, 7-ethoxycoumarin. The 7-ethoxycoumarin O- deethylation activity of hepatocytes was consistently higher than the activity measured with liver slices, when standardized by protein content of the two preparations. The metabolism of chloroform by hepatocytes isolated from male F344 rats was characterized by analyzing headspace and medium concentrations. The kinetic constants, estimated from the headspace data generated in these experiments, are K. 34 nmolflask and V max. 24 pmolmin106 cells. Headspace analysis was also useful for determining chloroform metabolism by liver slices. After addition of 3.6 nmolflask, the rate of chloroform loss was 2.5 pmolminmg tissue.
- Organic Chemistry