Lung aryl hydrocarbon hydroxylase: inhibition following cadmium chloride inhalation.
Polycyclic hydrocarbon metabolism in male Sprague-Dawley rats following inhalation of aerosolized cadmium chloride (CdCl2) was examined. Constitutive activity of microsomal aryl hydrocarbon hydroxylase (AHH) (benzo(a)pyrene substrate) was monitored in lung and liver homogenates up to 10 days after exposure. Lung AHH activity was reduced by 85% during the first 2 days following cadmium inhalation, and did not return to normal levels until 7 days after exposure. Enzyme activity in the livers of cadmium-treated animals was similarly depressed (by 65%) within 24 hr. Cadmium inhalation also inhibited (by 50%) 3-methylcholanthrene (MC) induction of lung AHH when compared with MC-treated controls. No significant effect on AHH inducibility by MC was noted in liver homogenates from cadmium-exposed animals. Nonspecific microsomal damage appeared not to occur since glucose-6-phosphatase activity in lung was unaffected by cadmium treatment. Although the mechanism of cadmium's action remains unclear, it appears not to involve a direct interaction of the metal with enzyme. The alteration of AHH activity by cadmium may result from injury to a specific cell type within the lung, which may be a major site of pulmonary AHH activity, or may result from modulation of synthesis and/or degradation of heme proteins in the lung. These results suggest that cadmium, under these conditions, markedly reduces the constitutive and inducible activity of AHH in the lung.
D000336:Aerosols; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D019256:Cadmium Chloride; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
D000336:Aerosols; D002104:Cadmium; D001189:Aryl Hydrocarbon Hydroxylases; D005952:Glucose-6-Phosphatase; D019256:Cadmium Chloride