The quantitation of liver cytochrome P450-LM2 mRNA in rabbits of different ages and after phenobarbital treatment.

Using very young (neonate or 0 day), 50-, 100-, 300- and 830-day-old rabbits we have studied changes in liver drug-metabolizing activities. Total liver microsomal cytochrome P450 content, benzphetamine N-demethylase and 7-ethoxycoumarin O-deethylase activities all decline with increasing age. When the rabbits of different age groups were pretreated with phenobarbital, liver microsomal enzyme activities increased in each group as compared with its control, but the total induced activities still decreased with increasing age. Using a specific assay for translatable cytochrome P450-LM2 mRNA, we show that the age-dependent decrease in control and phenobarbital-induced enzyme activities is due to a decrease in the levels of translatable mRNA specific for cytochrome P450-LM2. This is the first report on an age-dependent decrease in the level of a specific translatable mRNA. We do not know whether this decrease is due to decreased mRNA synthesis, or increased mRNA degradation.