TY - JOUR A1 - Herbst, Uta A1 - Fuchs, Iris Judith A1 - Teubner, Wera A1 - Steinberg, Pablo T1 - 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 N2 - 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. Y1 - 2006 UR - http://www.sciencedirect.com/science/journal/0041008X U6 - https://doi.org/10.1016/j.taap.2005.07.016 SN - 0041-008X ER - TY - JOUR A1 - Hacker, Hans-Jörg A1 - Steinberg, Pablo A1 - Bannasch, Peter T1 - 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 Y1 - 1998 ER - TY - JOUR A1 - Mueller, Carsten A1 - Ullmann, Kristina A1 - Wilkens, Andrea A1 - Winterhalter, Peter A1 - Toyokuni, Shinya A1 - Steinberg, Pablo T1 - Potent antioxidative activity of vineatrol (R) 30 grapevine-shoot extract N2 - 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. Y1 - 2009 UR - http://www.jstage.jst.go.jp/browse/bbb U6 - https://doi.org/10.1271/Bbb.90213 SN - 0916-8451 ER - TY - JOUR A1 - Müller, Carsten A1 - Ullmann, Kristina A1 - Steinberg, Pablo T1 - The grapevine-shoot extract Vineatrol30 Inhibits the chemically induced malignant transformation of BALB/c-3T3 Cells JF - Journal of medicinal food N2 - 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. KW - BALB/c-3T3 cells KW - cell transformation assay KW - resveratrol KW - resveratrol oligomers KW - Vineatrol (R) 30 Y1 - 2011 U6 - https://doi.org/10.1089/jmf.2010.0022 SN - 1096-620X VL - 14 IS - 1-2 SP - 34 EP - 39 PB - Liebert CY - New Rochelle ER - TY - JOUR A1 - Steinberg, Pablo A1 - Zschaler, Ingrid A1 - Thom, Elke A1 - Kuna, Manuela A1 - Wüst, Günter A1 - Schäfer-Schwebel, Angelika A1 - Müller, Rolf A1 - Kramer, Peter-Jürgen A1 - Weiße, Günter T1 - The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses Y1 - 2001 UR - http://www.springerlink.com/content/100462 U6 - https://doi.org/10.1007/s002040100274 SN - 0340-5761 ER - TY - JOUR A1 - Komlosh, A. A1 - Volohonsky, Gloria A1 - Porat, Noga A1 - Tuby, chen n. y. h. A1 - Bluvshtein, Evgenia A1 - Steinberg, Pablo A1 - Oesch, Franz A1 - Stark, Avishay Abraham T1 - Gamma-glutamyl transpeptidase and glutathione biosynthesis in non-tumorigenic and tumorigenic rat liver oval cell lines Y1 - 2001 ER - TY - JOUR A1 - Hengstler, Jan Georg A1 - Utesch, D. A1 - Steinberg, Pablo T1 - Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction Y1 - 2000 ER - TY - JOUR A1 - Schleger, C. A1 - Heck, R. A1 - Steinberg, Pablo T1 - The role of wild-type and mutated N-ras in the malignant transformation of liver cells Y1 - 2000 ER - TY - JOUR A1 - Hengstler, Jan Georg A1 - Ringel, M. A1 - Biefang, Katja A1 - Hammel, S. A1 - Milbert, U. A1 - Gerl, M. A1 - Klebach, M. A1 - Diener, B. A1 - Platt, Karl-Ludwig A1 - Böttger, Thomas A1 - Steinberg, Pablo A1 - Oesch, Franz T1 - Cultures with cryopreserved hepatocytes : applicability for studies of enzyme induction Y1 - 2000 ER - TY - JOUR A1 - Steinberg, Pablo A1 - Klingelhöffer, Alexandra A1 - Schäfer, Angelika A1 - Wüst, Günter A1 - Weiße, Günter A1 - Oesch, Franz A1 - Eigenbrodt, Erich T1 - Expression of pyruvate kinase M2 in preneoplastic hepatic foci of N-nitrosomorpholine-treated rats Y1 - 1999 ER -