Pulmonary toxicity caused by acute exposure to mercury vapor is enhanced in metallothionein-null mice.
This study examined the protective role of metallothionein (MT) against pulmonary damage caused by acute exposure to metallic mercury (Hg0) vapor using MT-null and wild-type mice. Both strains of mice were exposed to Hg0 at 6.6 to 7.5 mg/m3 for 4 hr each day for 3 consecutive days. This dosing protocol was lethal to over 60% of MT-null mice but did not kill any wild-type mice. More severe pulmonary damage was found by histopathological observation in MT-null mice than in wild-type mice. MT levels in the lung were elevated in wild-type mice after Hg0 vapor exposure, and gel filtration of the lung cytosol revealed that most of the mercury was associated with MT. In MT-null mice, MT levels were below the limit of detection (0.2 microg/g tissue) for the MT assay even after exposure. After exposure to Hg0 vapor for 3 consecutive days, the pulmonary mercury levels in wild-type mice were significantly higher than in MT-null mice. These findings suggest that MT plays a protective role against the acute pulmonary toxicity of Hg0 vapor.
Yoshida
M
M
Department of Chemistry, St. Marianna University School of Medicine, Kawasaki, Japan. m2yosida@marianna-u.ac.jp
Satoh
M
M
Shimada
A
A
Yasutake
A
A
Sumi
Y
Y
Tohyama
C
C
D000280:Administration, Inhalation; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002850:Chromatography, Gel; D003404:Creatinine / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011863:Radioimmunoassay; D015996:Survival Rate; D014835:Volatilization
D008668:Metallothionein; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008628:Mercury