6533b827fe1ef96bd12864fa

RESEARCH PRODUCT

The Distribution of Carcinogen Metabolizing Enzymes in the Mouse Liver: Comparison of Parenchymal and Non-Parenchymal Cell Populations

Pablo SteinbergFranz OeschW. M. Lafranconi

subject

chemistry.chemical_classificationMetabolismOxidative phosphorylationMolecular biologystomatognathic diseaseschemistry.chemical_compoundEnzymeBenzo(a)pyrenechemistryotorhinolaryngologic diseasesInducerEpoxide hydrolaseReceptorCarcinogen

description

The distribution of aminopyrine N-demethylase (APND), ethoxy- resorufin O-deethylase (ERRD), epoxide hydrolase (EH) and glutathione transferase (GST) activities in parenchymal (PC) and non-parenchymal (NPC) cell populations of control and Aroclor 1254-treated C57BL/6N and DBA/2N mice was determined. Furthermore, the metabolism of benzo(a)- pyrene (BP) in PC and NPC of both Aroclor 1254-treated mice strains was examined. Measurable activities of all enzymes investigated were detected in control PC as well as NPC of both mice strains; in all instances the PC possessed greater enzyme activities than did the NPC. The PC and NPC of DBA/ 2N mice had significantly lower ERRD and EH activities than PC and NPC of C57BL/6N mice. In NPC of both strains a low ratio of oxidative (APND and ERRD) to post-oxidative (EH and GST) enzyme activities was observed. Hence, NPC of C57BL/6N and DBA/2N mice might have a relatively lower ability to oxidize xenobiotics to reactive electrophiles and a greater ability to conjugate or hydrolyze those products that may be formed. Treatment with Aroclor 1254 enhanced all the enzyme activities measured in PC and NPC of both mice strains with the exception of ERRD in PC and NPC of DBA/2N mice. This is due to the fact that the induction process of ERRD by aromatic and halogenated aromatic compounds such as Aroclor 1254 depends upon the presence of a cytosolic receptor with a high affinity for this type of inducers and the DBA/2N mice have a very poor affinity receptor. After incubating BP with PC or NPC of Aroclor 1254-treated C57BL/6N mice significant amounts of 9,10-dihydrodiol, 4,5-dihydrodiol, 7,8-dihydrodiol, quinone, 9-hydroxy and 3-hydroxy derivatives of BP were detected. In contrast trace to non-detectable levels of the dihydrodiol derivatives were observed in PC as well as NPC of DBA/2N mice.

https://doi.org/10.1007/978-3-642-71617-1_13