scispace - formally typeset
Search or ask a question
Author

Franz Oesch

Bio: Franz Oesch is an academic researcher from University of Mainz. The author has contributed to research in topics: Epoxide hydrolase & Microsomal epoxide hydrolase. The author has an hindex of 76, co-authored 578 publications receiving 21684 citations. Previous affiliations of Franz Oesch include University of Basel & National Institutes of Health.


Papers
More filters
Journal ArticleDOI
Franz Oesch1
TL;DR: Whether a given aromatic or olefinic compound produces such an effect would depend on a variety of factors, such as the relative rate of formation and degradation of the intermediate oxirane, on its stability with respect to spontaneous isomerization to the corresponding phenol and on its chemical electrophilic reactivity.
Abstract: 1. Several aromatic and olefinic compounds are converted to intermediate arene and alkene oxides by mammalian mono-oxygenases. Intermediate arene oxides rearrange non-enzymically to phenols. Arene and alkene oxides are converted by epoxide hydrases to vicinal diols and by glutathione S-epoxide conjugases to glutathione conjugates. Due to their high electrophilic reactivity, such oxiranes also bind to proteins, RNA and DNA. Mutagenic, carcinogenic and cytotoxic effects of several aromatic and olefinic compounds appear to be due to the formation of intermediate epoxides and their reaction with tissue constituents. Whether a given aromatic or olefinic compound produces such an effect would thus depend on a variety of factors, such as the relative rate of formation and degradation of the intermediate oxirane, on its stability with respect to spontaneous isomerization to the corresponding phenol and on its chemical electrophilic reactivity.2. Epoxide hydrases, which convert such intermediate oxiranes t...

805 citations

Journal ArticleDOI
TL;DR: The simplicity of the present assay permits the use of epoxide hydrase a a marker enzyme for microsomal membranes in hepatic microsomes increases during maturation of rats and following pretreatment of rats with phenobarbital or 3-methylcholanthrene.

407 citations

Journal ArticleDOI
TL;DR: It is concluded that experiences with other, non-nano, substances taught us that mechanisms of genotoxic effects can be diverse and their elucidation can be demanding, while there often is an immediate need to assess the genotoxicity hazard.
Abstract: Nanomaterials display novel properties to which most toxicologists have not consciously been exposed before the advent of their practical use. The same properties, small size and particular shape, large surface area and surface activity, which make nanomaterials attractive in many applications, may contribute to their toxicological profile. This review describes what is known about genotoxicity investigations on nanomaterials published in the openly available scientific literature to-date. The most frequently used test was the Comet assay: 19 studies, 14 with positive outcome. The second most frequently used test was the micronucleus test: 14 studies, 12 of them with positive outcome. The Ames test, popular with other materials, was less frequently used (6 studies) and was almost always negative, the bacterial cell wall possibly being a barrier for many nanomaterials. Recommendations for improvements emerging from analyzing the reports summarized in this review are: Know what nanomaterial has been tested (and in what form); Consider uptake and distribution of the nanomaterial; Use standardized methods; Recognize that nanomaterials are not all the same; Use in vivo studies to correlate in vitro results; Take nanomaterials specific properties into account; Learn about the mechanism of nanomaterials genotoxic effects. It is concluded that experiences with other, non-nano, substances (molecules and larger particles) taught us that mechanisms of genotoxic effects can be diverse and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus a practical, pragmatic approach is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands adaptations and the interpretation of results from the genotoxicity tests may need additional considerations. This review should help to improve standard genotoxicity testing as well as investigations on the underlying mechanism and the interpretation of genotoxicity data on nanomaterials.

356 citations

Journal ArticleDOI
TL;DR: The results suggest that strategies enhancing the expression of MHC class I and tumor‐associated antigens need to be considered in attempts at making vaccination more effective.
Abstract: Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.

318 citations


Cited by
More filters
Journal Article
TL;DR: In soil, fertilizers containing inorganic nitrogen and wastes containing organic nitrogen are first decomposed to give ammonia, which is then oxidized to nitrite and nitrate, which are taken up by plants and used in the synthesis of organic nitrogenous compounds.
Abstract: In soil, fertilizers containing inorganic nitrogen and wastes containing organic nitrogen are first decomposed to give ammonia, which is then oxidized to nitrite and nitrate. The nitrate is taken up by plants during their growth and used in the synthesis of organic nitrogenous compounds. Surplus nitrate readily moves with groundwater (2, 3). Under aerobic conditions, it percolates in large quantities into the aquifer because of the small extent to which degradation or denitrification occurs. Under anaerobic conditions, nitrate may be denitrified or degraded almost completely to nitrogen. The presence of high or low water tables, the amount of rainwater, the presence of other organic material, and other physicochemical properties are also important in determining the fate of nitrate in soil ( 4). In surface water, nitrification and denitrification may also occur, depending on the temperature and pH. The uptake of nitrate by plants, however, is responsible for most of the nitrate reduction in surface water. Nitrogen compounds are formed in the air by lightning or discharged into it from industrial processes, motor vehicles, and intensive agriculture. Nitrate is present in air primarily as nitric acid and inorganic aerosols, as well as nitrate radicals and organic gases or aerosols. These are removed by wet and dry deposition.

4,627 citations

Journal ArticleDOI
TL;DR: The biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress, and to allow identification of factors that may modulate resistance to specific noxious chemicals.
Abstract: The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

3,516 citations

Journal ArticleDOI
01 Aug 2004-Immunity
TL;DR: The full understanding of the immunobiology of cancer immunosurveillance and immunoediting will hopefully stimulate development of more effective immunotherapeutic approaches to control and/or eliminate human cancers.

2,550 citations

Journal ArticleDOI
TL;DR: Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells.

2,424 citations

Journal ArticleDOI
TL;DR: Some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment are discussed, and the methods for implementing them are discussed.
Abstract: The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.

2,182 citations