A mechanism for the loss of cytochrome P-450 in primary mouse hepatocytes |
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Authors: | Gurmit Singh Karen L Veltri |
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Institution: | (1) Department of Pathology, Ontario Cancer Foundation, Hamilton Regional Cancer Centre and McMaster University, L8N 3Z5 Hamilton, Ontario, Canada;(2) Department of Pathology, HSC 3N26D, McMaster University, 1280 Main Street West, L8N 3Z5 Hamilton, Ontario, Canada |
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Abstract: | This study examined various biochemical parameters such as mitochondria and mitochondrial DNA (mtDNA), total heme and cyto P450 content in fresh hepatocytes and dedifferentiated hepatocytes. These parameters were chosen in order to understand the dramatic decrease in drug metabolism in cultured hepatocytes. The data in this study shows a temporal decrease in cytochrome P450, total heme and also a decrease in mitochondria. Also, the ratio of mtDNA content to mitochondrial density was found to increase as hepatocytes underwent dedifferentiation. Stereological analysis of cell preparations provided a measure of mitochondrial density per cell area and mtDNA content was assessed by the use of a specific radiolabelled probe. This study demonstrates that a loss of the organelle which is partially responsible for synthesis of heme correlates with a decrease in cytochrome P450. |
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Keywords: | cytochrome P-450 mitochondria heme hepatocytes mitochondrial DNA cell culture |
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