EXPRESSION OF CYP1A1 AND CYP1A2 GENES IN HUMAN LIVER

Immunoblot analysis of human livers using a monospecific antibody to r at CYP1A2 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 m RNAs in human liver. Hepatic content of CYP1A2 mRNA correlated signifi cantly with levels of CYP1A2 protein as analysed by immunoblot analysi s (r = 0.58; p < 0.01). CYP1A2 mRNA content varied >40-fold among indi viduals while CYP1A1 content varied >20-fold. CYP1A2 mRNA was higher t han CYP1A1 mRNA (approximately two to 30-fold) in livers of different individuals. The individual with the highest CYP1A1 and CYP1A2 mRNA am ounts was a current smoker, but mRNA expression in two other smokers w as within the range observed among nonsmokers. The expression of the t wo 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 prote in. Sequence analysis indicated that exon 4 was missing in this clone, but no other sequence changes were found. PCR analysis demonstrated t hat both the normally spliced mRNA and abnormally spliced mRNA could b e detected in all human livers examined, but the normally spliced mRNA was more abundant than the splice variant. Therefore, sequence change s in the coding region of CYP1A2 did not account for the poor expressi on of CYP1A2 in this individual.