Burt R K, Thorgeirsson S S
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
J Natl Cancer Inst. 1988 Nov 2;80(17):1383-6. doi: 10.1093/jnci/80.17.1383.
The levels of mRNA for multidrug-resistance (MDR-1) and selective cytochrome P-450 genes were determined in adult rat liver following administration of various natural and synthetic xenobiotics. MDR-1 (also known as PGY1) was induced following administration of aflatoxin B1, 2-(acetylamino)fluorene (AAF), N-hydroxy-2-(acetylamino)fluorene, isosafrole, phenothiazine, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but not after phenobarbital or 7-hydroxy-2-(acetylamino)fluorene treatment. Cytochrome P-450 isoform d was induced by TCDD, isosafrole, phenothiazine, and AAF, while cytochrome P-450 isoform b was induced by phenobarbital, and to a lesser extent by isosafrole. These observations suggest that both MDR and cytochrome P-450 gene families are evolutionarily selected by the capacity of various xenobiotics to induce their own detoxification either through metabolism to hydrophilic derivatives by the cytochrome P-450 system or direct excretion from the cell by the MDR gene family. Furthermore, the data indicate that induction of selective members of the MDR and the cytochrome P-450 gene families may depend on overlapping regulatory elements.
在给成年大鼠施用各种天然和合成的外源化学物后，测定了多药耐药性（MDR-1）和选择性细胞色素P-450基因的mRNA水平。在施用黄曲霉毒素B1、2-（乙酰氨基）芴（AAF）、N-羟基-2-（乙酰氨基）芴、异黄樟素、吩噻嗪和2,3,7,8-四氯二苯并对二恶英（TCDD）后，MDR-1（也称为PGY1）被诱导，但在苯巴比妥或7-羟基-2-（乙酰氨基）芴处理后未被诱导。细胞色素P-450同工型d被TCDD、异黄樟素、吩噻嗪和AAF诱导，而细胞色素P-450同工型b被苯巴比妥诱导，异黄樟素的诱导程度较小。这些观察结果表明，MDR和细胞色素P-450基因家族在进化上都是由各种外源化学物通过细胞色素P-450系统代谢为亲水性衍生物或由MDR基因家族直接从细胞中排泄来诱导自身解毒的能力所选择的。此外，数据表明，MDR和细胞色素P-450基因家族的选择性成员的诱导可能取决于重叠的调控元件。
