Covalent binding of o,p'-DDD in rabbit lung and isolated rabbit lung cells.
The irreversible binding of o,p'-DDD was examined in isolated lung cells, in lung microsomes and in vivo in male New Zealand White rabbits. Non-ciliated bronchiolar (Clara) cells had the highest capacity to bind o,p'-DDD, followed by alveolar type II cells. A fraction of mixed unidentified lung cells was also able to bind o,p'-DDD while no binding was observed in alveolar macrophages. The activation of o,p'-DDD was shown to be mediated by cytochrome P-450 in both lung microsomes and isolated lung cells. In vivo, the binding was preferentially localized in the lung alveolar and bronchiolar regions. The binding of o,p'-DDD observed in vivo may thus be caused by the capacity of several cell types to activate o,p'-DDD.
Lund
B O
BO
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala Biomedical Center.
Becher
R
R
Låg
M
M
Dahl
J E
JE
D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007672:Kidney Cortex / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008939:Mitotane / Q000008:administration & dosage / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011817:Rabbits
D065607:Cytochrome P-450 Enzyme Inhibitors; D008939:Mitotane