Exacerbation of benzene pneumotoxicity in connexin 32 knockout mice: enhanced proliferation of CYP2E1-immunoreactive alveolar epithelial cells.
The pulmonary pathogenesis triggered by benzene exposure was studied. Since the role of the connexin 32 (Cx32) gap junction protein in mouse pulmonary pathogenesis has been suggested, in the present study, we explored a possible role of Cx32 in benzene-induced pulmonary pathogenesis using the wild-type (WT) and Cx32 knockout (KO) mice. The mice were exposed to 300 ppm benzene by inhalation for 6 h per day, 5 days per week for a total of 26 weeks, and then sacrificed to evaluate the pneumotoxicity or allowed to live out their life span to evaluate the reversibility of the lesions and tumor incidence. Our results clearly revealed exacerbated pneumotoxicity in the benzene-exposed Cx32 KO mice, characterized by diffuse granulomatous interstitial pneumonia, markedly increased mucin secretion of bronchial/bronchiolar and alveolar epithelial cells, and hyperplastic alveolar epithelial cells positive for CYP2E1. But the results did not indicate any enhancement of pulmonary tumorigenesis in the Cx32 KO mice though the number of animals was small.
Yoon
Byung-Il
BI
Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagayaku, Tokyo 158-8501, Japan.
Hirabayashi
Yoko
Y
Kawasaki
Yasushi
Y
Tsuboi
Isao
I
Ott
Thomas
T
Kodama
Yukio
Y
Kanno
Jun
J
Kim
Dae-Yong
DY
Willecke
Klaus
K
Inoue
Tohru
T
D000280:Administration, Inhalation; D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D017630:Connexins / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
D001554:Benzene; D017630:Connexins; D019392:Cytochrome P-450 CYP2E1; D009077:Mucins; D018809:Proliferating Cell Nuclear Antigen; D000097002:Gap Junction beta-1 Protein