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
Source: PubMed


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.

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    • "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. "

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