EFFECTS OF CARBARYL AND NAPHTHALENE ON RAT HEPATIC CYP1A1 2 - POTENTIAL BINDING TO AH RECEPTOR AND 4S BENZO(A)PYRENE-BINDING PROTEIN/

Activation of the CYP1A1 gene has been described to be mediated by the cytosolic Ah receptor (AhR) and a possible cooperative role of the 4S benzo(a)pyrene-binding protein (4S protein). Carbaryl (CAR) has been shown to induce human CYP1A1 gene expression without binding to the hu man AhR. In this study, Sprague-Dawley rats received a single i.p. dos e of 20, 80, 150 mu mol/kg CAR or NAPn (naphthalene, the aromatic part of CAR) and were sacrificed after 24 h. CAR increased ethoxyresorufin -O-deethylase and methoxyresorufin-O-demethylase activities, the level of CYP1A1, 1A2 proteins, and CYP1A1 mRNA at the highest dose, whereas NAPn showed no effects. Moreover, CAR, naphthol (its major metabolite ) and NAPn were not ligands in vitro of the TCDD binding site of AhR o r the benzo(a)pyrene binding site of 4S protein in rat, neither was CA R a ligand of these two binding sites in mice, dog, monkey or human. M olecular properties of CAR were evaluated and showed that this molecul e is far from the structural characteristics of CYP1A1 specific induce rs although a planar conformation can be achieved with an energy <5 kJ .mol(-1). The data demonstrated that CAR could also modulate the AhR-m ediated responses, even though it did not meet the structural requirem ents to be ligand of AhR.