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A number of xenobiotics require biotransformation to exert their toxicities. Reactive metabolites may exert their toxic effects either directly in the cell or may be released to cause a toxic effects either directly in the cell or may be released to cause a toxic effect on other organs and cells. Cells of the blood system were chosen as first target cells for this transcellular toxicity. Genetically engineered cells expressing CYP isoforms were used a s the metabolism system and were treated with cyclophosphamide. Direct metabolism-medicated toxicity was measured by neutral red uptake and trypan blue exclusion. For detecting transcellualr metabolism-medicated toxicity, a six-step in vitro co-culture approach was established by using effects on cytokine release as a sensitive endpoint. The aim is to investigate the use of genetically engineered cell lines expressing drug metabolizing enzymes.

Additional information

Authors: IHCP, ;JRC-ISPRA (IT),
Bibliographic Reference: Paper presented: Third world congress on alternatives and animal use in the life sciences, Bologna (IT), 2nd September (1999)
Availability: Available free of charge from Public Relations and Publications Unit, Ispra (IT)
Record Number: 199911445 / Last updated on: 1999-10-01
Original language: en
Available languages: en
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