Detection of mRNA encoding xenobiotic-metabolizing cytochrome P450s in human bronchoalveolar macrophages and peripheral blood lymphocytes.
Human pulmonary tissue are known to contain enzymes mediating procarcinogen activation. Peripheral blood lymphocytes and bronchoalveolar macrophages (BAMs) have been used as surrogates for the lung in studies involving cytochrome P450 (CYP) parameters, including CYP1A1 inducibility in relation to susceptibility to lung cancer. In this study, a comprehensive view of the expression patterns of xenobiotic-metabolizing CYP forms in human BAMs and peripheral blood lymphocytes was obtained by using gene-specific reverse transcriptase-polymerase chain reaction analysis. These patterns were compared with that in the whole lung. mRNAs of CYP2B6/7, CYP2C, CYP2E1, CYP2F1, CYP3A5, and CYP4B1 were detected in all seven BAM samples studied; however, only the mRNA of CYP2E1 was found consistently in all eight lymphocyte samples. The amounts of amplification products of CYP2B6/7, CYP2C, CYP3A5, and CYP4B1 were low and inconsistent, indicating low levels of expression in lymphocytes. Consistent with previous knowledge, mRNAs of CYP1A1, CYP2B6/7, CYP2E1, CYP2F1, CYP3A5, and CYP4B1 were detected in whole-lung tissue. These results give an overall picture of the expression of CYP genes in the xenobiotic-metabolizing families CYP1, CYP2, and CYP3 in BAMs, peripheral blood lymphocytes, and whole-lung tissue and will aid in directing future studies on the respective protein products. The differences in the CYP gene expression patterns between lung and lymphocytes cast additional doubt on the use of lymphocytes as a surrogate for the lung.
Hukkanen
J
J
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Hakkola
J
J
Anttila
S
S
Piipari
R
R
Karjalainen
A
A
Pelkonen
O
O
Raunio
H
H
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System