The distribution of carcinogen metabolizing enzymes in the mouse liver: comparison of parenchymal and non-parenchymal cell populations.
The distribution of aminopyrine N-demethylase (APND), ethoxyresorufin 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Steinberg
P
P
Lafranconi
W M
WM
Oesch
F
F
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D004851:Epoxide Hydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010088:Oxidoreductases / Q000378:metabolism; D014018:Tissue Distribution
D001140:Aroclors; D002273:Carcinogens; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases