Aryl hydrocarbon hydroxylase represents CYP1B1, and not CYP1A1, in human freshly isolated white cells: trimodal distribution of Japanese population according to induction of CYP1B1 mRNA by environmental dioxins.
The expression level of mRNAs for cytochrome P450 (CYP) 1A1 and 1B1 in freshly prepared white cells from 72 subjects exposed to dioxins at waste incinerators was investigated. The amounts of CYP1B1 mRNA ranged from 0.16 to 671 molecules/10(7) molecules of 18S rRNA, whereas the amounts of CYP1A1 mRNA were <6 molecules/10 ng total RNA, indicating that CYP1A1 was not induced to a detectable level by environmentally exposed dioxins. The inducibility of CYP1B1 mRNA in leukocytes, defined as the ratio of CYP1B1 mRNA to the plasma concentration of dioxins, varied among the subjects. It was found that the subjects showed trimodal distribution according to inducibility: 39 (54.2%), 25 (34.7%), and 8 (11.1%) of 72 subjects were judged as poor, intermediate, and high responders to environmental dioxins, respectively. The amounts of CYP1B1 mRNA in leukocytes of the intermediate and high responders were highly correlated with the plasma concentrations of dioxins (P < 0.05 and <0.01). These results suggest that CYP1B1 with polymorphic inducibility by dioxins is involved in aromatic hydrocarbon hydroxylase activities in human lymphocytes.
Toide
Kenji
K
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Yamazaki
Hiroshi
H
Nagashima
Rikako
R
Itoh
Keisuke
K
Iwano
Shunsuke
S
Takahashi
Yoshiki
Y
Watanabe
Shaw
S
Kamataki
Tetsuya
T
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004147:Dioxins / Q000009:adverse effects*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D017745:Incineration; D007564:Japan; D007962:Leukocytes / Q000378:metabolism; D016273:Occupational Exposure / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics*
D004147:Dioxins; D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1