Distinct subtypes of urinary bladder epithelial cells with inducible and non-inducible cytochrome P450 1A1
Leibniz Research Centre for Working Environment and Human Factors, Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo), Ardeystr. 67, 44139 Dortmund, Germany. Archives of Toxicology
(Impact Factor: 5.98).
02/2009; 83(2):131-8. DOI: 10.1007/s00204-008-0329-3
Cultured primary porcine urinary bladder epithelial cells (PUBEC) represent an adequate and easy to handle in vitro system for studies of urothelial toxicity. PUBEC maintain in vivo-like metabolic activities and physiological functions. They express inducible cytochrome P4501A isoenzymes, which are of particular relevance, since they contribute to activation of bladder carcinogens. A possible drawback of PUBEC is their isolation from common domestic pigs that do not represent an inbred strain. In order to further establish PUBEC as a standard in vitro toxicity test system we analysed possible interindividual differences in CYP1A1 inducibility. Interestingly, we observed by flow cytometry that PUBEC obtained from individual pigs consist of two distinct subpopulations with inducible and non-inducible cells. A strong, concentration-dependent CYP1A1 induction was observed in the responsive subpopulation when incubated with benzo[a]pyrene (B[a]P) in a concentration range between 1 and 10 muM. In contrast, no CYP1A1 induction was obtained in the non-responsive subpopulation up to the highest tested concentrations of 100 muM. The fraction of responsive cells showed large interindividual differences ranging from 10 to 65% of the total cell number. For practical purposes it might be reasonable to analyse pools of PUBEC from five pigs which substantially reduce batch to batch variability. In conclusion, we have identified two functionally distinct subpopulations of urinary bladder epithelial cells. It will be interesting to study whether the CYP1A inducible subtype is more susceptible to bladder carcinogens.
Available from: Joanna D Stewart
- "Furthermore, as caspase 9 and 3 are activated but caspase 8 and 10 are not, apoptosis is therefore induced via the mitochondrial pathway. Since both, reactive oxygen species (Bolt and Hengstler 2010; Nishimura et al. 2010; Cederbaum et al. 2009; Wang et al. 2009a, b; Schumann et al. 2009; Schug et al. 2008; Glahn et al. 2008) and apoptosis (Han and Park 2010; Ogata et al. 2010; Wang et al. 2009a, b; Plöttner et al. 2009; Borza et al. 2008; Lehmann et al. 2010) represent cutting-edge topics of our journal, the current review may be of high interest to our readers. Moreover, the authors have reviewed 17 clinical studies on prophylaxis of contrast agent-induced nephrotoxicity. "
Available from: Sabine Plöttner
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ABSTRACT: Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes.
Available from: eldorado.tu-dortmund.de
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ABSTRACT: Current research in carcinogenesis is focussed on enzymes controlling reactive compounds and the maintenance of DNA integrity. An outstanding example is a review on epoxide hydrolases. known to be key enzymes in detoxification of carcinogenic epoxides (Decker et al., 2009). However, it has recently become clear that besides their function in xenobiotic metabolism, epoxide hydrolases also play a role in signal transduction and inflammatory control. A further highlight is a review on telomeres and the mechanisms that avoid the misinterpretation of chromosome ends as sites of DNA breaks. The table gives a brief overview of the key messages of recent studies in the field of carcinogenesis.
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