Cytochrome p450 gene expression levels in peripheral blood mononuclear cells in comparison with the liver.
Cytochromes p450 (CYPs) compose a superfamily of similar proteins involved in detoxification and elimination, as well as activation of a wide variety of compounds. Most CYP family members are localized in the liver. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for the determination of CYP gene expression levels in the liver, we compared CYP gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, 3A7, 4A11, 4B1 and CYP27 gene expressions in PBL and in the liver by real-time reverse-transcription (RT)-PCR. We could detect expression of CYP1A1, 1A2, P1B1, 2A6, 2B6 and 2E1 genes in PBL and all the genes except for CYP2F1 in the liver. Although gene expression levels within each subfamily were closely correlated within PBL and within the liver, a clear correlation of gene expression levels between PBL and liver tissues was found only for CYP4B1. Although inter-individual variation of the expression level of each CYP gene was wide, the induced level was proportional to the basal expression level. Therefore, monitoring of CYP gene expression levels in PBL, especially those of CYP4B1, could be available as a biomarker for monitoring of exposure to environmental pollutants and assessing the associated risk. Compared with non-tumor tissue, HCC tissues tended to show overexpression of multiple CYP genes, indicating that individualized selection and more effective administration of chemotherapeutic agents could perhaps be based on the pattern of CYP overexpression.
Furukawa
Motonobu
M
Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan.
Nishimura
Masuhiro
M
Ogino
Daisuke
D
Chiba
Ryoji
R
Ikai
Iwao
I
Ueda
Nobuhiko
N
Naito
Shinsaku
S
Kuribayashi
Shunji
S
Moustafa
Mohsen A
MA
Uchida
Takafumi
T
Sawada
Hideki
H
Kamataki
Tetsuya
T
Funae
Yoshihiko
Y
Fukumoto
Manabu
M
D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System