72-kDa stress protein (Hsp72) induced by administration of dimethylarsinicacid 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 dime thylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, in mice causes DNA damage in the lung as well as the promotion and progres sion of lung- and skin-tumorigenesis. Moreover, we indicated that 72-kDa st ress 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 ad ministration of DMA to A/J mice used preciously as an animal model of dimet hylarsenic-induced lung tumorigenesis. The Hsp72 was observed in the lung. a target organ for arsenic carcinogenesis in human, and in the kidney as we ll, but not in the Liver and spleen. By immunohistochemical analysis, the H sp72 in lungs was exhibited to exist in the nuclei of alveolar Bat cells, i ncluding capillary endothelial cells, which were previously found to increa se the clumping of heterochromatin, an early morphological change in the de velopmental process of pulmonary carcinomas, after administration of DMA to mice. These in vivo observations suggest that the increase and accumulatio n of Hsp72 by administration of DMA to mice may occur specifically in targe t organs for arsenic carcinogenesis.