Changes of silver-stained nucleolar organizer regions in mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-oestradiol.

A high incidence of endometrial adenocarcinoma and pre-neoplastic lesions was induced in ICR mice treated with N-methyl-N-nitrosourea and 17 beta-oestradiol within 23 weeks. The endometrial lesions were histopathologically similar to those of human subjects. To assess the cell proliferative activity of these lesions, a one-step silver colloid staining for nucleolar organizer regions was applied and the numbers of silver-stained nucleolar organizer regions (AgNORs) were counted. The mean numbers +/- SD of AgNORs in each lesion were as follows: simple hyperplasia, 2.07 +/- 0.36; complex hyperplasia without cytological atypia, 2.79 +/- 0.39; complex hyperplasia with cytological atypia, 3.43 +/- 0.38; and well-differentiated adenocarcinoma, 4.17 +/- 0.40. Significant differences were observed in each lesion (P < 0.001). These findings suggest that the mean numbers of Ag-NORs are increased in the progression of neoplastic changes in the mouse endometrium, as in human endometrial lesions. This rapid induction model of endometrial carcinoma in mice is useful in the understanding of the histogenesis of endometrial carcinoma in human subjects.