@article{SchulzThierbachVoigtetal.2006,
  author    = {Schulz, Tim Julius and Thierbach, Ren{\`e} and Voigt, Anja and Drewes, Gunnar and Mietzner, Brun and Steinberg, Pablo and Pfeiffer, Andreas F. H. and Ristow, Michael},
  title     = {Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited},
  doi       = {10.1074/jbc.M511064200},
  year      = {2006},
  abstract  = {More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich ataxia-associated protein frataxin in several colon cancer cell lines. These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content. Consistent with Warburg's hypothesis, we found that frataxin-overexpressing cells also have decreased growth rates and increased population doubling times, show inhibited colony formation capacity in soft agar assays, and exhibit a reduced capacity for tumor formation when injected into nude mice. Furthermore, overexpression of frataxin leads to an increased phosphorylation of the tumor suppressor p38 mitogen-activated protein kinase, as well as decreased phosphorylation of extracellular signal-regulated kinase. Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals},
  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{SinghSinghDanietal.2005,
  author    = {Singh, Jasbir and Singh, S. and Dani, H. M. and Sharma, Reeta and Steinberg, Pablo},
  title     = {Interactions of aflatoxin B-1 with SRP components can disrupt protein targeting},
  issn      = {0263-6484},
  year      = {2005},
  abstract  = {Spectrofluorimetric studies have revealed that aflatoxin B-1 (AFB(1)) interacts with signal recognition particle (SRP), which acts as an escort for polyribosomes with signal peptides to be transported and bound to the cytoplasmic face of the endoplasmic reticulum (ER). We further report that the binding of AFB(1) to SRP is selective as it only binds to two (SRP9 and 14) out of its three constituent polypeptides studied. Binding of AFB(1) to proteins is known to alter their conformations. Interactions of AFB(1) with SRP polypeptides may generate structural and functional alterations in this particle and hinder secretory protein synthesis. Copyright (C) 2004 John Wiley Sons, Ltd},
  language  = {en}
}
@article{ThierbachSchulzIskenetal.2005,
  author    = {Thierbach, Ren{\`e} and Schulz, Tim Julius and Isken, Frank and Voigt, Aanja and Mietzner, Brun and Drewes, Gunnar and von Kleist-Retzow, J{\"u}rgen-Christoph and Wiesner, Rudolf J. and Magnuson, Mark A. and Puccio, Helene and Pfeiffer, Andreas F. H. and Steinberg, Pablo and Ristow, Michael},
  title     = {Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice},
  year      = {2005},
  abstract  = {We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals},
  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{TeubnerLangheinrichSeideletal.2004,
  author    = {Teubner, Wera and Langheinrich, C. and Seidel, Albrecht and Steinberg, Pablo},
  title     = {Inhibition of p53 transactivation activity does not promote mutagen-induced transformation of IEC-18},
  issn      = {0028-1298},
  year      = {2004},
  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{ThierbachSchulzVoigtetal.2004,
  author    = {Thierbach, Rene and Schulz, Tim Julius and Voigt, Aanja and Drewes, Gunnar and Isken, F. and Pfeiffer, Andreas F. H. and Ristow, Michael and Steinberg, Pablo},
  title     = {Targeted disruption of frataxin in hepatocytes causes spontaneous neoplasia accompanied by increased ROS formation},
  issn      = {0028-1298},
  year      = {2004},
  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{StarkPoratVolohonskyetal.2003,
  author    = {Stark, Avishay abraham and Porat, Noga and Volohonsky, Gloria and Konlosh, A. and Bluvshtein, Evgenia and Tubi, C. and Steinberg, Pablo},
  title     = {The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione},
  year      = {2003},
  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{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{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{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{VolohonskyTubyPoratetal.2002,
  author    = {Volohonsky, Gloria and Tuby, Chen N. Y. H. and Porat, Noga and Wellman-Rousseau, Maria and Visvikis, Athanase and Leroy, Pierre and Rashi, Sharon and Steinberg, Pablo and Stark, Avishay Abraham},
  title     = {A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione synthetase in crude extracts from tissues and cultured mammalian cells},
  year      = {2002},
  language  = {en}
}
@article{SteinbergZschalerThometal.2001,
  author    = {Steinberg, Pablo and Zschaler, Ingrid and Thom, Elke and Kuna, Manuela and W{\"u}st, G{\"u}nter and Sch{\"a}fer-Schwebel, Angelika and M{\"u}ller, Rolf and Kramer, Peter-J{\"u}rgen and Weiße, G{\"u}nter},
  title     = {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},
  issn      = {0340-5761},
  doi       = {10.1007/s002040100274},
  year      = {2001},
  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{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{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}
}
@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}
}