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Research focus:  

Lehrstuhl für Toxikologie
Versbacher Str. 9, 97078 Würzburg
Mail: lutz@toxi.uni-wuerzburg.de
Url: http://www.uni-wuerzburg.de/toxikologie/

Scientific members:

   Professors:

   Outside lecturer:

   Scientific assistants:

Research foci (and basic equipment-based research projects):
Chemical Carcinogenicity.

The research focuses on elucidating the mutagenic and carcinogenic effects
of chemicals, with the aim of a cancer risk characterization.
Investigations include biotransformation (metabolic activation and
detoxification of chemical carcinogens; Prof. Dekant), the induction of
primary DNA damage (DNA adduct formation; Prof. Eder), cytogenetics studies
(Prof. Stopper) and aspects of cell differentiation (Dr. Bitsch). A wide
range of assay for genotoxicity testing (DNA adducts, DNA single- and
double-strand breaks, micronucleus formation) and mutagenicity testing
(Ames test, mouse lymphoma assay, SSCP) is available. In the field of human
biomonitoring, adduct formation plays a major role (hemoglobin binding,
Prof. Neumann; DNA adducts, Prof. Lutz).
Two new research groups in immunotoxicology (Dr. Fischer) and
neurotoxicology (Dr. Götz) are being established.


Toxic Substances investigated

Exposures at the workplace, through the diet, and via the environment are
considered. The list of chemicals includes polycyclic aromatic
hydrocarbons, aromatic amines, nitroaromatic compounds, chlorinated
aliphatic chemicals (haloalkenes), plastic monomers (styrene, isocyanates,
butadiene), fragrances. Diet-related carcinogens comprise ochratoxin,
anthranoids and polyphenols, as well as different types of fat and their
peroxidation products, such as unsaturated aldehydes. Phytoestrogens and
xenoestrogens, including their metabolites, are investigated with respect
to a hormonal contribution to the process of carcinogenesis.


Questions addressed

Risk characterization is based on hazard identification,
dose-response-relationships, and exposure evaluation. In order to carry out
the necessary extrapolations in a biologically founded manner, the mode of
carcinogenic action has to be known. Extrapolations are required from
experimental systems to humans, from high dose to low dose, from a
homogenous group of experimental animals to the heterogeneity of a human
population. The analysis of the sequence from external exposure - internal
concentration - biochemical effect - biological effect - clinical
manifestation is part of the dose-effect relationship and is followed by
means of biological monitoring.
Endogenous and unavoidable DNA-damaging agents and processes contribute to
spontaneous cancer incidence. Oxidative stress is investigated as a major
factor. The cancer risk associated with an exogenous exposure has to be put
in relation to the background DNA damage.

Results:
Bayer, T., Amberg, A., Bertermann, R., Rusch, G. M., Anders, M.W., and Dekant, W.: Biotransformation of 1,1,1,3,3-Pentafluoropropane (HFC-245fa). Chem. Res. Toxicol. (2002) 15, 723-733.
Budiawan and Eder, E.: Detection of 1,N2-propanodeoxyguanosine adducts in Fischer 344 rats by an adapted 32P-postlabeling technique after gavage of crotonaldehyde. Carcinogenesis (2000) 21, 1191-1196.
Fischer, W.H., Keiwan, A., Schmitt, E., and Stopper, H.: Increased formation of micronuclei after hormonal stimulation of cell proliferation in human breast cancer cells. Mutagenesis (2001) 16 (3), 209-212.
Lutz, W.K., Vamvakas, S., Kopp-Schneider, A., Schlatter, J., Stopper, H.: Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation. Environ. Health Perspect. (2002) 110 (Suppl. 6).
Lutz, W.K.: Dose-response relationships in chemical carcinogenesis and cancer risk assessment. In: Genetic Toxicology and Cancer Risk Assessment (ed. Choy, W. N.). Marcel Dekker New York (2001) 249-270.
Oesch, F., Herrero, M.E. , Hengstler, J.G., Lohmann, M., Arand, M: Metabolic detoxification: implications for thresholds. Toxicol. Pathol. (2000) 28, 382-387.
Oesch, F., Herrero, M.E., Lohmann, M., Hengstler, J.G., Arand, M.: Sequestration of biological reactive intermediates by trapping as covalent enzyme-intermediate complex. Adv. Exp. Med. Biol. (2001) 500, 577-586.
Stopper, H., Boullay, F., Bahner, U., Vienken, J., and Heidland, A.: Comet-assay analysis shows genomic damage in lymphocytes of patients with pre-endstage renal failure and after longterm maintenance hemodialysis therapy. American J. Kidney Disease (2001) 38(2), 296-301.
Völkel, W., Colnot, T. Csanady, G. A., Filser, J. G. and Dekant, W.: Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. Chem. Res. Toxicol. (2002) 15, 1281-1287.
Wacker, M., Wanek, P., Eder, E., Hylla, S., Gostner, A. and Scheppach, W.: Effects of enzyme-resistent starch on formation of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal and cell proliferation in the colonic mucosa of healthy volunteers. Cancer Epidem. Biomarkers Prev. (2002) 11, 915-920.