The influence of age on the inducibility of rat liver cytochrome P450IA1 (CYPIA1) and P450IA2 (CYPIA2) mRNAs.
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.
Horbach
G J
GJ
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Van Asten
J G
JG
Van Bezooijen
C F
CF
D000375:Aging / Q000235:genetics*; D000818:Animals; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004790:Enzyme Induction; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D010088:Oxidoreductases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D012451:Safrole / Q000494:pharmacology
D012333:RNA, Messenger; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D012451:Safrole; C015959:isosafrole