Significant Increase In Mitotic Index Research Articles

Process of repair in the neuroepithelium of developing rat brain during neurogenesis: chronological and quantitative observation of DNA-replicating cells

The neuroepithelium (NE) of the cerebrum of the developing brain has been reported to `regenerate' within a certain period after being injured. To clarify the process of repair of the NE during neurogenesis, we chronologically examined the number of cells in the neocortex, and the rate of DNA-replicating cells and the mitotic figure ratio in the NE of rats after injury. The injury was induced by transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to the pregnant rats on embryonic day 16. The number of living and pyknotic cells in a 220- μm width of the neocortex was evaluated in each of three groups, such as NE, subventricular zone (SVZ)+intermediate zone (IMZ)+subplate (SP), and cortical plate (CP). The 5-bromo-2-deoxyuridine (BrdU)-labeling index and the mitotic index were examined 4, 8, 16, 24, 36, and 48 h after ENU administration. Up to 16 h after ENU administration, the number of living cells per 220 μm width in the NE and SVZ+IMZ+SP decreased, but increased in CP. From 16 to 24 h, the living cell number per 220 μm width in the NE and CP was unchanged, but increased in the SVZ+IMZ+SP. From 24 to 36 h, the living cell number per 220 μm width increased in all the groups, NE, SVZ+IMZ+SP and CP. From 36 to 48 h, the living cell number per 220 μm width in the NE was unchanged, but increased in the SVZ+IMZ+SP and CP. The BrdU-labeling index reached its nadir at 8 h, but markedly increased by 16 h, and then decreased to the control level by 36 h. No mitotic figures were observed at 16 h after administration, but a significant increase in mitotic index was noted at 24 h, and after which it decreased to almost the control value by 36 h. These findings indicate: (i) that temporary arrest of neuroepithelial cell cycle occurs in the G 1-phase from 4 to 8 h after ENU administration, (ii) that the cell cycle synchronizes in the S-phase at 16 h, (iii) that a proportion of neuroepithelial cells of rat fetal neocortex at the neurogenesis stage return to neuroepithelial cell proliferation stage, to repair the NE, and (iv) that regulation of the cell kinetics of neuroepithelial cells depends on the number of cells in a certain width of NE during regeneration.

Effects of androgen manipulations on chemically induced colonic tumours and on macroscopically normal colonic mucosa in male Sprague-Dawley rats

Epidemiological and experimental studies suggest that androgens influence colonic carcinogenesis. We investigated the effects of hormonal manipulations (surgical and chemical castration, hormone substitution) on colonic tumour development, tumour and mucosal histopathology, and epithelial proliferation in macroscopically normal colonic mucosa in male rats, after induction of chemical colon carcinogenesis by subcutaneous injections of azoxymethane (AOM). Chemical castration with cyproterone acetate, but not surgical castration, resulted in increased colonic tumorigenesis, which was accompanied by decreased crypt length, decreased number of cells per crypt, and increased crypt epithelial mitotic index in the right colon. Chemically castrated rats also had crypt hyperplasia and increased numbers of dysplastic foci in the left colon which were not seen with surgical castration. By contrast, rats given testosterone after surgical castration showed decreased colonic tumorigenesis with an increased proportion of tumours in the left colon and lower percentage of tumours with invasion. The grossly normal mucosa of the testosterone-substituted castrated rats showed decreased crypt length in the right colon similar to the other groups of castrated rats, but no significant increase in mitotic index. Our results suggest that the anti-androgenic progestin cyproterone is a potent enhancer of colonic tumorigenesis and epithelial proliferative abnormalities after AOM administration. Exogenous testosterone after castration alters tumour distribution and characteristics and suppresses epithelial proliferative abnormalities. Finally, androgen effects on the colonic mucosa are more prominent in the right than in the left colon, suggesting different influences of hormones on the epithelium of these anatomical sites.