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Immunoblot analysis of human livers using a monospecific antibody to rat CYP1 A2§ demonstrated that the expression of CYP1A2 protein is highly variable in human liver. Quantitative PCR analysis was then employed to examine the interindividual variability of both CYP1A1 and CYP1A2 mRNAs in human liver. Hepatic content of CYP1A2 mRNA correlated significantly with levels of CYP1A2 protein as analysed by immunoblot analysis (r=0.58; p<0.01). CYP1A2 mRNA content varied>40-fold among individuals while CYP1 Al content varied>20-fold. CYP1A2 mRNA was higher than CYP1 Al mRNA (approximately two to 30-fold) in livers of different individuals. The individual with the highest CYP1A1 and CYP1A2 mRNA amounts was a current smoker, but mRNA expression in two other smokers was within the range observed among nonsmokers. The expression of the two CYP1A mRNAs correlated highly (r=0.72; p<0.0005) when smokers were included, but the correlation was less significant (r =0.62; p<0.05) in nonsmokers. We amplified a full-length CYP1A2 cDNA clone by PCR from a liver which expressed extremely low amounts of CYP1A2 protein. Sequence analysis indicated that exon 4 was missing in this clone, but no other sequence changes were found. PCR analysis demonstrated that both the normally spliced mRNA and abnormally spliced mRNA could be detected in all human livers examined, but the normally spliced mRNA was more abundant than the splice variant. Therefore, sequence changes in the coding region of CYP1A2 did not account for the poor expression of CYP1A2 in this individual.