Abstract
Feline kidney cells were transfected with a vector overexpressing cytochrome P450 2B1 (CYP2B1). Transfected cells acquired a new specific biochemical activity, which could be demonstrated by a rapid CYP2B1 detection assay and showed selective sensitivity to the antitumorigenic prodrug ifosfamide (IFO). Further, the cell-killing effect was also mediated on nonmodified cells like feline kidney cells, mouse lymphoma, and human pancreatic cells in the vicinity of the CYP2B1-expressing cells due to the diffusible nature of the activated IFO metabolites. One of these, phosphoramide mustard, causes interstrand DNA cross-linking and it has been thought that the inability to repair this damage results in apoptosis. Surprisingly, our results clearly demonstrate a necrotic mechanism of IFO-induced cell death. This may have important implications for the activation of the immune system during CYP2B1/IFO suicide gene therapy of cancer. Cancer Gene Therapy (2001) 8, 220–230
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Karle, P., Renner, M., Salmons, B. et al. Necrotic, rather than apoptotic, cell death caused by cytochrome P450–activated ifosfamide. Cancer Gene Ther 8, 220–230 (2001). https://doi.org/10.1038/sj.cgt.7700290
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DOI: https://doi.org/10.1038/sj.cgt.7700290
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