Horbach G J, Van Asten J G, Van Bezooijen C F
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Mutat Res. 1990 May-Jul;237(3-4):117-21. doi: 10.1016/0921-8734(90)90017-l.
The levels of the messenger RNAs for the cytochromes P450IA1 (CYPIA1) and P450IA2 (CYPIA2) were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either 3-methylcholanthrene or isosafrole and in untreated rats. An increase in the CYPIA1 mRNA levels was observed only after treatment with 3-methylcholanthrene, whereas both 3-methylcholanthrene and isosafrole were able to induce the levels of CYPIA2 mRNA. The study presented here shows that the maximal induction of these 2 mRNAs did not change with age when 3-methylcholanthrene was used as the inducing agent. Isosafrole induction did not yield higher CYPIA1 mRNA levels in young rats but reduced the amount of this mRNA in old animals to levels below the detection limit of our assay. After induction with isosafrole the levels of the CYPIA2 mRNAs in the older age groups were lower than those observed in young rats. It is concluded that with age the responsiveness to cytochrome P450 inducers may change. This change is different for the various cytochrome P450 enzymes and depends on which inducer is used.
在用3 - 甲基胆蒽或异黄樟素最大程度诱导后，以及在未处理的大鼠中，测定了不同年龄大鼠肝脏细胞质RNA中细胞色素P450IA1（CYPIA1）和P450IA2（CYPIA2）信使RNA的水平。仅在用3 - 甲基胆蒽处理后观察到CYPIA1 mRNA水平增加，而3 - 甲基胆蒽和异黄樟素均能诱导CYPIA2 mRNA水平。此处呈现的研究表明，当使用3 - 甲基胆蒽作为诱导剂时，这两种mRNA的最大诱导作用不会随年龄而改变。异黄樟素诱导在幼鼠中未产生更高的CYPIA1 mRNA水平，但在老年动物中将该mRNA的量降低至我们检测方法的检测限以下。在用异黄樟素诱导后，老年组中CYPIA2 mRNA的水平低于幼鼠中观察到的水平。得出的结论是，随着年龄增长，对细胞色素P450诱导剂的反应性可能会发生变化。这种变化因不同的细胞色素P450酶而异，并且取决于使用哪种诱导剂。
