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See detailMitogen-Activated Lymphocytes: A Good Model for Characterising Lung Cyp1a1 Inducibility
Lambert, Vincent ULg; Todaro, Anna ULg; Kremers, Pierre ULg et al

in European Journal of Epidemiology (1997), 13(2), 177-83

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility ... [more ▼]

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility factor, generally evaluated on mitogen-activated lymphocytes after PAH induction, represents correctly the lung situation. Optimal experimental conditions were determined for evaluating, on both lymphocytes and lung tissue explants, the inducibility factor, defined as the ratio of EROD activity (CYP1A1-specific) to cytochrome c reductase activity (unaffected by PAH induction). Paired results for lymphocytes and lung tissue samples from 10 lung cancer patients were compared. A good correlation was observed between lymphocyte and lung tissue inducibilities (R = 0.809; p = 0.005). In conclusion, mitogen-activated lymphocyte inducibility is indicative of lung tissue inducibility and constitutes a good marker for evaluating individual PAH inducibilities. [less ▲]

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See detailEffect of Inducers and Pcbs on the Cytochrome P450 Enzymes in Cultured Quail Hepatocytes
Roelandt, L.; Dubois, Maryline; Todaro, Anna ULg et al

in Ecotoxicology & Environmental Safety (1995), 31(2), 158-63

Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were cultured in vitro. Their capacity to metabolize drugs and xenobiotics was explored with typical cytochrome P450 substrates ... [more ▼]

Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were cultured in vitro. Their capacity to metabolize drugs and xenobiotics was explored with typical cytochrome P450 substrates: ethoxycoumarin (known to be metabolized by several P450s), ethoxyresorufin (essentially dealkylated by P450IA1), and testosterone (specifically hydroxylated at several positions by several P450s). The cells could be kept metabolically active in culture for at least 4 days. Their drug-metabolizing activities were inducible by the usual P450 inducers, like phenobarbital and benzanthracene, but also by Aroclor 1254, a PCB mixture. The results obtained indicate that this experimental model could certainly be very helpful in ecotoxicological studies. [less ▲]

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See detailEffects of Pcbs (Aroclor 1254) on Cytochrome-P450 Expression and Monooxygenase Activities in Cultured Foetal Rat Hepatocytes
Roelandt, L.; Todaro, Anna ULg; Thomé, Jean-Pierre ULg et al

in Toxicology (1995), 98(1-3), 95-103

Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used ... [more ▼]

Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used as target cells constitute an interesting in vitro model for studying the mechanisms of action of PCBs. In this paper, and the accompanying one (Toxicology 98 (1995) 83-94), we have used this model to investigate the effects of PCBs on several cellular parameters. The inducibility of CYPIA1 is the most sensitive parameter studied, as shown by the induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities at PCB concentrations as low as 1 microM. Dexamethasone treatment of the cells potentiates this induction. PCB induction is reversible and occurs even in cells cultured for several days. CYP2B and CYP3A seem unaffected by PCBs in this experimental system. By inducing CYP1A1, PCBs can trigger the 'activation' of xenobiotics, such as polycyclic hydrocarbons, into mutagenic compounds. [less ▲]

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