Roos P H, Belik R, Föllmann W, Degen G H, Knopf H J, Bolt H M, Golka K
Institute for Occupational Physiology at the University of Dortmund (IfADo), Ardeystr. 67, 44139 Dortmund, Germany.
Arch Toxicol. 2006 Jan;80(1):45-52. doi: 10.1007/s00204-005-0026-4. Epub 2005 Dec 10.
Expression of cytochromes P450 CYP1A1, CYP1B1, CYP2E1 and CYP4B1 was analysed on the transcript level in human urothelial cells obtained by various methods. As a source of urothelial cells, exfoliated cells in urine samples were used. Their expression profiles were determined either immediately after centrifugal enrichment (n=4) or after their cultivation and propagation (n=8). Another source of urothelial cells were ureter specimens from surgical subjects (n=4). Generally, expression was most prominent for CYP1B1 and CYP4B1 among the CYP transcripts analysed. CYP1B1 mRNA was detected in all samples investigated except for one ureter specimen. CYP4B1 mRNA was present in cell cultures from three out of eight healthy subjects, in three out of four directly investigated urinary sediments and in the cells of all five ureter specimens of four donors investigated after resection and subsequent cell culture. In most cases, CYP2E1 transcript levels were lower than those of CYP1B1 and CYP4B1. CYP2E1 mRNA was detected in cell cultures of six out of eight healthy subjects, in one out of four urinary sediments and in three out of five ureter specimens. CYP1A1 mRNA was clearly observed only in cells from resected ureters. In cell cultures the relative mRNA expression levels varied with subjects interindividually, intraindividually and also during the time of cell culture. The study demonstrates constitutive mRNA expressions of xenobiotic metabolising CYP enzymes in human urothelial cells obtained by different methods. In particular, transcripts of CYP1B1 and CYP4B1 are present, coding for enzymes which are active in the metabolism of polycyclic aromatic hydrocarbons and arylamines, respectively.
通过多种方法获取的人尿道上皮细胞中，对细胞色素P450 CYP1A1、CYP1B1、CYP2E1和CYP4B1的表达进行了转录水平分析。作为尿道上皮细胞的来源，使用了尿液样本中的脱落细胞。它们的表达谱在离心富集后立即测定（n = 4）或在培养和增殖后测定（n = 8）。另一个尿道上皮细胞来源是手术对象的输尿管标本（n = 4）。一般来说，在所分析的CYP转录本中，CYP1B1和CYP4B1的表达最为显著。除了一个输尿管标本外，在所有研究的样本中均检测到CYP1B1 mRNA。在八名健康受试者中的三名的细胞培养物中、四名直接检测的尿沉渣中的三名以及四名供体的所有五个输尿管标本切除后并随后进行细胞培养的细胞中，均存在CYP4B1 mRNA。在大多数情况下，CYP2E1转录水平低于CYP1B1和CYP4B1。在八名健康受试者中的六名的细胞培养物中、四名尿沉渣中的一名以及五名输尿管标本中的三名中检测到CYP2E1 mRNA。仅在切除的输尿管细胞中清楚地观察到CYP1A1 mRNA。在细胞培养物中，相对mRNA表达水平在个体间、个体内以及细胞培养期间均有所不同。该研究证明了通过不同方法获得的人尿道上皮细胞中异源生物代谢CYP酶的组成型mRNA表达。特别是，存在CYP1B1和CYP4B1的转录本，分别编码在多环芳烃和芳基胺代谢中具有活性的酶。
