Intergroup Research Initiative
Urothelium and Chemical Toxicity [UroTox]
Coordination: PD Dr. rer. nat. Peter H. Roos
Aims and cooperating groups
This intergroup activity links experimental research on chemical toxicities in urinary bladder and kidney with questions posed on cancer risk factors for these target organs in an occupational medicine context. Scientists from three research groups "Chemical risks" (Degen, Föllmann), "Molecular toxicology " (Roos), "Systems toxicology" (Hengstler) and two central support units "Clinical Occupational Medicine" (Golka) and "Analytical Chemistry" (Blaszkewicz) with different academic backgrounds participate, and thus cover biochemical, cell biological, occupational medicine and toxicological aspects. The different viewpoints (e. g. disease-oriented, mechanism- or compound-oriented) feed into a transdisciplinary dialogue and promote synergy effects, as exemplified by joint project proposals and publications (see below).
Contents and activities
Previous and ongoing work at IfADo on culturing and characterizing urogenital tract and kidney cells from both animals and humans provides a focal point for the constitution of the intergroup activity „UroTox“. These cells are used in studies with chemicals known or suspected as cancer risk factors for the target organs kidney and urinary bladder. Research activities span from investigations on the mode of action of certain agents to those on human exposure in occupational and other contexts. Of special interest are molecular targets for chemical toxicities, in order to gain insight into the pathogenetic process and aid in identifying suitable biomarkers (of exposure, effect and susceptibility). In this respect, supplementary information is obtained also from studies with established urothelial and kidney cell lines. To achieve the goals, a broad spectrum of methods is made available by the cooperating groups (see respective pages of the research groups involved).
There are regular meetings of the research inititiative including PhD students to discuss research progress, ideas and planning of future projects including the following topics:
- toxicological studies concerning the effects of selected compounds such as aromatic amines, polycyclic aromatic hydrocarbons and mycotoxins;
- primary effects of chemicals on the system of xenobiotic metabolizing enzymes and associated signaling pathways;
- effects of carcinogens on components of signal transduction pathways and of cell cycle control
- impact of genetic polymorphisms with respect to toxic and carcinogenic effects on urothelial cells (phase I and II enzymes, transporter, regulatory proteins);
- development of methods and in vitro model systems (cell lines, cell separation);
- problems and aspects of occupational medicine (exposure).
Selected publications
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Borza A, Plöttner S, Wolf A, Behm C, Selinski S, Hengstler JG, Roos PH, Bolt HM, Kuhlmann J, Föllmann W (2008) Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes. Arch Toxicol 82, 973-980.
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Plöttner S, Degen GH, Roos PH, Föllmann W (2008) Analysis of CYP1A1 induction in single cells of urothelial cell populations by flow cytometry. Anal Bioanal Chem 392: 1149-1158.
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Roos PH, Golka K, Hengstler JG (2008) Predictive biomarkers and signatures in urinary bladder cancer. Curr Opin Mol Ther 10: 243-250.
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Dörrenhaus A, Müller T, Roos PH (2007) Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers. Arch Toxicol 81, 19-25.
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Roos PH, Belik R, Föllmann W, Degen GH, Knopf HJ, Bolt HM, Golka K (2006). Expression of cytochrome P450 enzymes CYP1A1, CYP1B1, CYP2E1, and CYP4B1 in non-invasively obtained transitional cells of the human urinary tract. Arch Toxicol 80: 45-52.
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Aslam M, Beg AE, Blaszkewicz M, Degen GH, Golka K (2005). Ochratoxin A blood concentration in healthy subjects and bladder cancer cases from Pakistan. Mycotoxin Res 21: 164-167.
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Degen GH, Lebrun S, Lektarau Y, Föllmann W (2005). Modulation of ochratoxin A induced DNA-damage in urothelial cell cultures. Mycotoxin Res 21: 57-60.
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Wolf A, Kutz A, Plöttner S, Behm C, Bolt HM, Föllmann W, Kuhlmann J (2005). The effect of benzo(a)pyrene on porcine urinary bladder epithelial cells analyzed for the expression of selected genes and cellular toxicological endpoints. Toxicology 207: 255-269.