Metallothionein induction and pulmonary responses to inhaled cadmium chloride in rats and mice.
Inhaled CdCl2 is a pulmonary carcinogen in rats but not in mice. We hypothesized that pulmonary metallothionein (MT) induction may be different in both species and thereby may lead to different levels of protection from Cd-induced lung injury. Fisher-344 rats and B6C3F1 mice were exposed for 4 weeks to CdCl2 aerosols of 0, 30, 50, and 150 micrograms/m3 air or 0, 10, 30, and 100 micrograms/m3 air, respectively. Animals from each exposure group were terminated at 1, 30 and 133 days after the end of exposure. The lungs were lavaged for cell and biochemical analyses. Cadmium and MT in lavagate and lung tissue were measured. The retention half-time of pulmonary Cd was greater in mice (290 vs 90 days, p < 0.05). Cd exposure provoked an inflammatory response which was dose-dependent in both species, and while it was only short-lived in rats, it persisted throughout the observation period in mice at the high exposure concentrations. Mice were found to have a greater baseline level of MT (18.04 +/- 6.96 vs 11.7 +/- 1.98 micrograms MT/g control lung, p < 0.05). Mice showed greater inducibility of MT for a given CdCl2 exposure concentration; however, both species had a similar relationship between retained pulmonary Cd and MT induction though mice maintained increased MT levels for a longer period of time. The greater pulmonary baseline MT together with the longer presence of Cd-induced pulmonary MT may result in greater protection from Cd carcinogenicity in spite of the greater pulmonary Cd-induced inflammation in mice.
Kenaga
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Department of Environmental Medicine and Dentistry, University of Rochester, New York 14642, USA.
Cherian
M G
MG
Cox
C
C
Oberdörster
G
G
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D019256:Cadmium Chloride; D002273:Carcinogens / Q000633:toxicity*; D002452:Cell Count; D002712:Chlorides / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D002273:Carcinogens; D002712:Chlorides; D002104:Cadmium; D008668:Metallothionein; D019256:Cadmium Chloride