Characteristic expression of aryl hydrocarbon receptor repressor gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells.
To investigate the expression of aryl hydrocarbon receptor repressor (AhRR) and related molecules in various tissues and the effects of aromatic hydrocarbons (AHs) on their expression, we developed a reliable technique of quantification of human AhRR as well as aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT) and cytochrome P450 1A1 (CYP1A1) mRNA by real-time TaqMan PCR method. First, we examined the expression of these genes in human adult or fetal tissues. The levels of AhRR expression were extremely high in testis, very high in lung, ovary, spleen and pancreas from adults, whereas those were low in those from fetuses. On the other hand, CYP1A1 expression was extremely high in lung, and AhR and ARNT were ubiquitously expressed in almost all tissues. Second, we compared the expression levels of these genes in mononuclear cells (MNCs) from various sources. Comparison of the basal expression levels of these genes in MNCs demonstrated that MNCs from umbilical cord blood showed higher AhRR or CYP1A1 expression than those from adults. The induction of AhRR or CYP1A1 expression by 3-methylcholanthrene (3-MC) was observed in MNCs from adults but not from umbilical cord blood. Consequently, there existed characteristic differences in the basal levels of AhRR and CYP1A1 expression in MNCs, as well as in their inducibility by 3-MC among MNCs from various types of human bloods. These results will provide basic information for a possible application of AhRR and CYP1A1 measurements to evaluate AH exposure in vivo.
Yamamoto
Junko
J
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan. jyamamoto@dr.hosp.kyushu-u.ac.jp
Ihara
Kenji
K
Nakayama
Hideki
H
Hikino
Shunji
S
Satoh
Kazuo
K
Kubo
Norio
N
Iida
Takao
T
Fujii
Yoshiaki
Y
Hara
Toshiro
T
D000328:Adult; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D002273:Carcinogens / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D004147:Dioxins / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004147:Dioxins; D008748:Methylcholanthrene; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D014157:Transcription Factors; C492162:AHRR protein, human; C497396:ARNT protein, human