Induction of gene expression of xenobiotic metabolism enzymes and ABC-transport proteins by PAH and a reconstituted PAH mixture in human Caco-2 cells

被引:51
作者
Lampen, A
Ebert, B
Stumkat, L
Jacob, J
Seidel, A
机构
[1] Tierarztlichen Hsch Hannover, Inst Lebensmitteltoxikol, D-30173 Hannover, Germany
[2] Prof Dr Gernot Grimmer Stiftung, Biochem Inst Umweltcarcinogene, D-22927 Grosshansdorf, Germany
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION | 2004年 / 1681卷 / 01期
关键词
benzo[a]pyrene; CYP1A1; CYP1B1; ABC-transporter; Caco-2; cell;
D O I
10.1016/j.bbaexp.2004.09.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It was shown recently that in epithelial Caco-2 cells the food contaminant benzo[a]pyrene (B[a]P) is metabolized and B[a]P-sulfate metabolites were transported out of the cells. The aim of this study was to investigate whether B[a]P and other polycyclic aromatic hydrocarbons (PAH) such as chrysene, phenanthrene, benzo[k]fluoranthene (B[k]F), dibenzo[a,l]pyrene (DB[a,l]P), and pyrene alone or in a mixture in a ratio as they occur in tobacco smoke have effects on gene expression of intestinal cytochrome P450 enzymes (CYP), Phase 11 enzymes and ATP-binding cassette (ABC)-transport proteins in the human Caco-2 cells. B[a] induced its own metabolism. Treatment of the Caco-2 cells with B[a]P, chrysene, B[k]F, or DB[a,I]P induced mRNA expression of CYP1A1 and CYP1B1 specifically as measured by RTPCR. In contrast, the mRNA expression of the microsomal epoxide hydrolase (mEH) was not affected by PAH. The gene expression of the Phase II enzymes UDP-glucuronosyltransferase 1A6 (UGT1A6) and UGT1A7 was also induced by these PAH but treatment with them had no effect on gene expression of sulfotransferases (SULT) at all. Of the ABC-transport proteins, MDR1 mRNA expression was induced by treatment with carcinogenic PAH, whereas MPP2 mRNA expression was not changed. The mixture of PAH also induced CYP1A1, CYP1B1, UGT1A6, and UGT1A7 mRNA expression. We conclude that B[a]P, chrysene, B[k]F, and DB[a,l]P have specific effects on intestinal CYP1A1, CYP1B1, UGT1A6, and UDP1A7 mRNA expression but no effects on the expression of SULT (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:38 / 46
页数:9
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