In vitro modulation of the P450 activities of hamster and human lung slices.
The respiratory tract is a portal of entry for many environmental chemicals. The respiratory tract plays an important role in the detoxification or metabolic activation of these chemicals, e.g., via cytochrome P450 enzymes. Alterations in the capabilities of these enzymes to metabolize inhaled compounds can, therefore, affect the toxicity of the chemicals. The pulmonary cytochrome P450 activity has been studied in many species, but relatively little is known about this activity in the human lung tissue. In this limited study, we have investigated the possibility of modulating in vitro the P450 activity in lung slices from hamsters and humans. The alkoxyresorufin-O-dealkylase activity was measured in the S9 fraction of lung slices incubated for 24 h with 10(6) mol/L 20-methylcholanthrene (3MC) or beta-naphthoflavone (beta N). The ethoxyresorufin-O-deethylase (EROD) activity was increased by 3MC and beta N in lung slices of both species. The benzyloxyresorufin-O-deethylase (BROD) activity was decreased after incubation with 3MC but increased with beta N. These data show that in vitro modulation in lung slices is feasible, although technical improvement is still needed, particularly in relation to the viability of the slices.
Hoet
P H
PH
K. U. Leuven, Laboratorium voor Pneumologie, Belgium.
Demedts
M
M
Nemery
B
B
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000633:toxicity; D019324:beta-Naphthoflavone / Q000633:toxicity
D065607:Cytochrome P-450 Enzyme Inhibitors; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1