72-kDa stress protein (hsp72) induced by administration of dimethylarsinic acid to mice accumulates in alveolar flat cells of lung, a target organ for arsenic carcinogenesis.
Our previous studies have demonstrated that the oral administration of dimethylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, in mice causes DNA damage in the lung as well as the promotion and progression of lung- and skin-tumorigenesis. Moreover, we indicated that 72-kDa stress protein (Hsp72) was induced in cultured human pulmonary (L-132) cells by exposure to DMA and was accumulated specifically in the cell nuclei. The present in vivo study reveals the induction of Hsp72 by intraperitoneal administration of DMA to A/J mice used previously as an animal model of dimethylarsenic-induced lung tumorigenesis. The Hsp72 was observed in the lung, a target organ for arsenic carcinogenesis in human, and in the kidney as well, but not in the liver and spleen. By immunohistochemical analysis, the Hsp72 in lungs was exhibited to exist in the nuclei of alveolar flat cells, including capillary endothelial cells, which were previously found to increase the clumping of heterochromatin, an early morphological change in the developmental process of pulmonary carcinomas, after administration of DMA to mice. These in vivo observations suggest that the increase and accumulation of Hsp72 by administration of DMA to mice may occur specifically in target organs for arsenic carcinogenesis.
Kato
K
K
Nihon University College of Pharmacy, Funabashi, Chiba, Japan. kohkato@pha.nihon-u.ac.jp
Yamanaka
K
K
Nakano
M
M
Hasegawa
A
A
Okada
S
S
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D015153:Blotting, Western; D002101:Cacodylic Acid / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002273:Carcinogens; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002101:Cacodylic Acid; D001151:Arsenic