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Early Changes Caused by N-Butyl-N-(4-hydroxybutyl)nitrosamine in the Bladder Epithelium of Different Animal Species¹

First Department of Pathology, Nagoya City University Medical School, Nagoya 467, Japan

Early changes in the bladder epithelium of male rats, mice, hamsters, and guinea pigs induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined.

Light microscopy showed that the normal mucosal epithelium of the distended bladder of rats, mice, hamsters, and guinea pigs was 2 to 4 cells thick. However, on treatment with BBN, the bladder epithelium increased diffusely to 5- to 8-cell thickness in rats and mice and 4- to 6-cell thickness in hamsters. It did not increase in thickness in guinea pigs. On treatment with BBN for 8 weeks, focal hyperplasia developed in the bladder epithelium of rats and mice, but the bladder epithelium of hamsters and guinea pigs did not change. Histological examination showed that the areas of focal hyperplasia in rats and mice had reduced alkaline phosphatase activity and increased nonspecific esterase and ß-glucuronidase activities. These activities did not change in the bladder epithelium of hamsters and guinea pigs treated with BBN.

Scanning electron microscopy showed that normally large, polygonal cells were present in the bladder epithelium of all these species. The luminal surface of the bladder of rats, mice, hamsters, and guinea pigs appeared to be covered with a network of fine ridges. After BBN treatment for 4 weeks, microvilli were seen on surface cells in rats, mice, and hamsters but not in guinea pigs. Cells in areas of focal hyperplasia in rats and mice appeared irregularly arranged and their surface was uneven with numerous microvilli.

By transmission electron microscopy, the cells on the surface of the normal bladder appeared clear, with numerous fusiform vesicles and free ribosomes in rats and mice but with few fusiform vesicles in hamsters and guinea pigs. On administration of BBN, the number of fusiform vesicles decreased in rats and mice but did not change in hamsters and guinea pigs. Areas of focal hyperplasia in rats and mice consisted of both dark and clear cells with few fusiform vesicles, and the cells had enlarged nuclei and nucleoli.

Thus, the difference in the susceptibilities of different animal species to urinary bladder carcinogenesis induced by BBN may be closely related to species differences in the changes induced in its fine structure.

¹ Presented at the Conference "Early Lesions and the Development of Epithelial Cancer," October 21 to 23, 1975, Bethesda, Md. This investigation was supported in part by Grants 001056, 001561, and 001062 (1975) from the Ministry of Education, Culture and Science, and by the Experimental Pathological Research Association, 1975.