@article{BarlowGreigBridgesetal.2002, author = {Barlow, S. M. and Greig, J. B. and Bridges, J. W. and Carere, A. and Carpy, A. J. and Galli, Corrado L. and Kleiner, J. and Knudsen, I. and Koeter, H. B. and Levy, L. S. and Madsen, C. and Mayer, S. and Narbonne, J. F. and Pfannkuch, F. and Prodanchuk, M. G. and Smith, Mason R. and Steinberg, Pablo}, title = {Hazard identification by methods of animal-based toxicology}, year = {2002}, language = {en} } @article{BartschZschalerHaseloffetal.2003, author = {Bartsch, Ingrid and Zschaler, Ingrid and Haseloff, Monika and Steinberg, Pablo}, title = {Establishment of a long-term culture system for rat colon epithelial cells}, issn = {1071-2690}, doi = {10.1290/0404035.1}, year = {2003}, abstract = {The aim of this study was to establish a long-term culture. system for rat colon epithelia isolaled by incubating a 4-cm-long rat colon segment cut longitudinally with all ethylenediaminetetraacetic acid [disodium salt]- containing buffer, taken up in conditioned medium from the normal rat kidney fibroblast cell line NRK (i.e., the supernatant Of pure NRK cultures), directly plated on mitomycin C-treated NRK cells and subcultured with conditioned medium from NRK cells. Cells started to migrate out of the crypts shortly after plating them on NRK feeder layers. Some of the crypts fell apart during the isolation procedure. whereas the vast majority of them did it within I to 2 Ill after plating. The cells proliferated extremely slowly but continuously over a period of 4 mo and were epithelial because they expressed cytokeratin 19 and were stained by crystal violet at pH 2.8. In conclusion, the experimental system described ill this study allows to maintain rat colon epithelial cells for up to 4 mo in culture and can be used to Study the effects of a variety of tumor-modulating factors on growth and gene expression of normal colon epithelial cells in vitro}, language = {en} } @article{BluvshteinGlassVolohonskyetal.1999, author = {Bluvshtein, Evgenia and Glass, George and Volohonsky, Gloria and Yaakubowitz, Margalit and Harness, Ella and Smorodinsky, Nechama and Seidel, Albrecht and Frank, Heinz and Stark, Avishay Abraham and Steinberg, Pablo}, title = {Inhibition of the hydrolytic and transpeptidatic activities of rat kidney gamma-glutamyltranspeptidase by specific monoclonal antibodies}, year = {1999}, language = {en} } @article{DybingDoeGrotenetal.2002, author = {Dybing, E. and Doe, J. and Groten, J. and Kleiner, J. and O'Brien, J. and Renwick, A. G. and Schlatter, J. and Steinberg, Pablo and Tritschler, A. and Walker, R. and Younes, M.}, title = {Hazard characterisation of chemicals in food and diet : dose response, mechanisms and extrapolation issues}, year = {2002}, language = {en} } @article{FuchsTeubnerSteinberg2004, author = {Fuchs, J. and Teubner, Wera and Steinberg, Pablo}, title = {The resistance of intestinal epithelial cells towards the transforming activity of 2-hydroxyamino-1-methyl-6- phenylimidazo[4,5-B]pyridine is accompanied by glutathione S-transferase induction}, issn = {0028-1298}, year = {2004}, language = {en} } @article{HackerSteinbergBannasch1998, author = {Hacker, Hans-J{\"o}rg and Steinberg, Pablo and Bannasch, Peter}, title = {Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine supplemented diet}, year = {1998}, language = {en} } @article{HengstlerRingelBiefangetal.2000, author = {Hengstler, Jan Georg and Ringel, M. and Biefang, Katja and Hammel, S. and Milbert, U. and Gerl, M. and Klebach, M. and Diener, B. and Platt, Karl-Ludwig and B{\"o}ttger, Thomas and Steinberg, Pablo and Oesch, Franz}, title = {Cultures with cryopreserved hepatocytes : applicability for studies of enzyme induction}, year = {2000}, language = {en} } @article{HengstlerUteschSteinberg2000, author = {Hengstler, Jan Georg and Utesch, D. and Steinberg, Pablo}, title = {Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction}, year = {2000}, language = {en} } @article{HengstlerVanDerBurgSteinbergetal.1999, author = {Hengstler, Jan Georg and VanDerBurg, Bart and Steinberg, Pablo and Oesch, Franz}, title = {Interspecies differences in cancer susceptibility and toxicity}, year = {1999}, language = {en} } @article{HerbstFuchsTeubneretal.2004, author = {Herbst, Uta and Fuchs, Iris Judith and Teubner, Wera and Seidel, Albrecht and Frank, Heinz and Steinberg, Pablo}, title = {Malignant transformation of human colon epithelial cells by polycyclic aromatic hydrocarbons and heterocyclic aromatic amines}, issn = {0028-1298}, year = {2004}, language = {en} } @article{HerbstFuchsTeubneretal.2006, author = {Herbst, Uta and Fuchs, Iris Judith and Teubner, Wera and Steinberg, Pablo}, title = {Malignant transformation of human colon epithelial cells by benzo[c]phenanthrene dihydrodiolepoxides as well as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine}, issn = {0041-008X}, doi = {10.1016/j.taap.2005.07.016}, year = {2006}, abstract = {Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) ingested with food have repeatedly been suggested to be involved in the malignant transformation of colon epithelial cells. In order to test this hypothesis, HCEC cells (SV40 large T antigen-immortalized human colon epithelial cells) were incubated with a racemic mixture of benzo[c]phenanthrene dihydrodiol epoxides (B[c]PhDE), extremely potent carcinogenic PAH metabolites in vivo, or with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), the N-hydroxylated metabolite of the most abundant HCA in cooked meat. First, it was shown that HCEC cells express sulfotransferase 1A1, which is needed to metabolize N-OH-PhIP to the corresponding N-sulfonyloxy derivative, the direct precursor molecule of genotoxic nitrenium ions. Thereafter, exponentially growing HCEC cells were exposed five times to 0.1 mu g (0.37 nmol) B[c]PhDE/ml for 30 min or 0.72 mu g (3 mnol) N-OH-PhTP/ml for 24 h. Chemically treated HCEC cells showed an enhanced saturation density and grew faster than the corresponding solvent-treated cell cultures. After five treatment cycles, HCECB[c]PhDE as well as HCECN-OH-PhIP cells lost cell-cell contact inhibition and started piling up and forming foci in the culture flasks. Furthermore, HCECB[c]phDE and HCECN-OH-PhIP cells were injected i.m. into SCID mice. Within 6 weeks after injection, eight animals out of eight injected with HCECB[c]phDE or HCECN-OH-PhIP cells developed tumors at the site of injection, thus demonstrating the high tumorigenic potential of the HCECB[c]PhDE and HCECN-OH-PhIP cell cultures. Taken together, we show for the first time that the abovementioned active PAH metabolites as well as N-OH-PhIP are indeed able to malignantly transform human colon epithelial cells in vitro.}, language = {en} } @article{KomloshVolohonskyPoratetal.2001, author = {Komlosh, A. and Volohonsky, Gloria and Porat, Noga and Tuby, chen n. y. h. and Bluvshtein, Evgenia and Steinberg, Pablo and Oesch, Franz and Stark, Avishay Abraham}, title = {Gamma-glutamyl transpeptidase and glutathione biosynthesis in non-tumorigenic and tumorigenic rat liver oval cell lines}, year = {2001}, language = {en} } @article{KuehnelSteinbergScholtka2004, author = {K{\"u}hnel, Dana and Steinberg, Pablo and Scholtka, Bettina}, title = {A human-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) can induce precancerous lesions in rat intestine after 6 months of exposure}, issn = {0028-1298}, year = {2004}, language = {en} } @article{MazurekEigenbrodtFailingetal.1999, author = {Mazurek, Sybille and Eigenbrodt, Erich and Failing, Klaus and Steinberg, Pablo}, title = {Alterations in the glycolytic and glutaminolytic pathways after malignant transformation of rat liver oval cells}, year = {1999}, language = {en} } @article{MuellerUllmannWilkensetal.2009, author = {Mueller, Carsten and Ullmann, Kristina and Wilkens, Andrea and Winterhalter, Peter and Toyokuni, Shinya and Steinberg, Pablo}, title = {Potent antioxidative activity of vineatrol (R) 30 grapevine-shoot extract}, issn = {0916-8451}, doi = {10.1271/Bbb.90213}, year = {2009}, abstract = {The health promoting effects of a grapevine-shoot extract named Vineatrol (R) 30, which contains resveratrol (Resv) as well as considerable amounts of Resv oligomers, have recently been investigated. In the present study, we analyzed the free radical scavenging capacity, the ability to inhibit lipid peroxidation, and the capacity to enhance the human glutathione peroxidase 1 (GPx) and the human superoxide dismutase 1 (SOD) gene promoter activities of Vineatrol (R) 30. Vineatrol (R) 30 was able to scavenge the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and led to concentration-dependent inhibition of lipid peroxidation, Vineatrol (R) 30 not being superior to Resv alone in both cases. Vineatrol (R) 30 also enhanced the gene promoter activities of human GPx and SOD expressed in V79 cells, whereas this effect could not be demonstrated for Resv. In summary, the results presented in this study show that the Vineatrol (R) 30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non- eytotoxic concentrations.}, language = {en} } @article{MuellerUllmannSteinberg2011, author = {M{\"u}ller, Carsten and Ullmann, Kristina and Steinberg, Pablo}, title = {The grapevine-shoot extract Vineatrol30 Inhibits the chemically induced malignant transformation of BALB/c-3T3 Cells}, series = {Journal of medicinal food}, volume = {14}, journal = {Journal of medicinal food}, number = {1-2}, publisher = {Liebert}, address = {New Rochelle}, issn = {1096-620X}, doi = {10.1089/jmf.2010.0022}, pages = {34 -- 39}, year = {2011}, abstract = {Vineatrol (R) 30 (developed and produced jointly by Breko GmbH [Bremen, Germany] and Actichem [Montauban, France]) is a grapevine-shoot extract that contains resveratrol as well as considerable amounts of resveratrol oligomers. In the present study it is shown that Vineatrol30 at a noncytotoxic concentration of 2.3 mu g/mL significantly reduced the number of malignantly transformed foci induced by a sequential treatment of BALB/c-3T3 cells with 3-methylcholanthrene and 12-O-tetradecanoylphorbol 13-acetate in the so-called BALB/c-3T3 cell transformation assay. At a higher concentration Vineatrol30 drastically decreased the relative plating efficiency of the cells. Furthermore, the results suggest that the resveratrol oligomers present in Vineatrol30, independently from resveratrol itself, were indeed able to inhibit the formation of malignantly transformed BALB/c-3T3 foci.}, language = {en} } @article{OkanoShiotaMatsumotoetal.2003, author = {Okano, J. and Shiota, G. and Matsumoto, K. and Yasui, S. and Kurimasa, A. and Hisatome, I. and Steinberg, Pablo and Murawaki, Y.}, title = {Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway}, year = {2003}, language = {en} } @article{SchlegerBeckerOeschetal.1999, author = {Schleger, C. and Becker, Rolf and Oesch, Franz and Steinberg, Pablo}, title = {The human p53 gene mutated at position 249 per se is not sufficient to immortalize human liver cells}, year = {1999}, language = {en} } @article{SchlegerHeckSteinberg2000, author = {Schleger, C. and Heck, R. and Steinberg, Pablo}, title = {The role of wild-type and mutated N-ras in the malignant transformation of liver cells}, year = {2000}, language = {en} } @misc{ScholtkaKuehnelTaugneretal.2009, author = {Scholtka, Bettina and K{\"u}hnel, Dana and Taugner, Felicitas and Steinberg, Pablo}, title = {Inflammation does not precede or accompany the induction of perneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44570}, year = {2009}, abstract = {Heterocyclic aromatic amines (HCAs) are formed in meat cooked at high temperatures for a long time or over an open flame. In this context 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HCA in cooked meat, has been suggested to be involved in colon and prostate carcinogenesis. In the latter case it has been reported that: (1) roughly 50\% of Fischer F344 male rats treated with PhIP develop carcinomas in the ventral prostate lobe at 1 year of age; (2) inflammation precedes prostatic intraepithelial neoplasia in PhIP-fed rats; (3) inflammation specifically occurs in the ventral prostate lobe of PhIP-fed rats. To test whether PhIP by itself leads to inflammation in the colon and whether a human-relevant concentration of PhIP is able to induce preneoplastic lesions in the colon, male F344 rats were fed 0.1 or 100 ppm PhIP for up to 10 months and thereafter the colon tissue was analyzed histochemically. In none of the experimental groups signs of acute or chronic colonic inflammation were observed. 0.1 ppm PhIP leads to the development of hyperplastic and dysplastic lesions in the colon of single animals, but the incidence of these lesions does not reach a statistical significance. In contrast, in rats fed 100 ppm PhIP for 10 months hyperplastic and dysplastic colonic lesions were induced in a statistically significant number of animals. It is concluded that: (1) the induction of preneoplastic lesions in rat colon by PhIP is not preceded or accompanied by an inflammatory process; (2) a human-relevant concentration of PhIP alone is not sufficient to initiate colon carcinogenesis in rats.}, language = {en} }