Suppression of multi-drug resistance gene expression in the mouse liver by 1,4-bis[2,(3,5-dichloropyridyloxy)]benzene
✍ Scribed by Alison L. Russell; Colin J. Henderson; Gillian Smith; C. Roland Wolf
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 569 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
P-glycoproteins encoded by the (multi-drug resistance) mdr genes play a central role in the resistance of tumor cells to a wide range of anti-cancer drugs. Modulation of P-glycoprotein function could therefore provide a means of sensitising tumor cells to chemotherapy. Studies in this context have centred around the use of compounds which antagonise the Pglycoprotein membrane transport system. To investigate the possibility of modulating P-glycoprotein expression at a transcriptional level, we investigated the effects of hormonal factors and cytochrome P45O-inducing agents on hepatic expression of murine mdr I, mdr 2 and mdr 3. Hepatic rndr 2 and mdr 3 expressions were significantly suppressed in hypophysectomised animals, indicating that pituitary hormones activate the hepatic expression of these genes. Many of the foreign compounds and anti-cancer drugs tested did not significantly induce mdr I, 2 or 3 expression. However, it was of particular interest that a potent cytochrome P450 inducer, I ,4-bis[2-(3,5dichloropyridyloxy)]benzene, almost completely suppressed hepatic mdr 2 and 3 expressions.