Difference in the Types of Uterine Tumors between Heterozygous p53-deficient and Wild Type CBA Mice Treated with Ethinylestradiol after N-ethyl-N-nitrosourea Initiation

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To cast light on the mechanisms of rapid induction of endometrial stromal sarcomas in p53-deficient CBA mice [p53 (+/-) mice] treated with ethinylestradiol (EE) after a single injection of N-ethyl-N-nitrosurea (ENU), p53 (+/-) and CBA/JNCrj mice [CBA mice] were given diet containing 2.5 ppm EE for 26 and 50 weeks, respectively, after ENU-initiation, and the types of uterine tumors induced were compared. Endometrial adenocarcinomas and stromal sarcomas were induced in 7% and 73%, respectively, of the p53 (+/-) mice given ENU followed by EE. In contrast, the CBA mice demonstrated incidences of adenocarcinomas and sarcomas of 100% and 25%, respectively. These results suggest that the uterine stromal cell is a major target cell of ENU-initiation in p53 (+/-) mice with a role for the tumor suppressor in governing its response to genetic damage due to ENU. The uterine epithelial cell is another target cell but subsequent long-term EE treatment appears prerequisite for the development of adenocarcinomas. While endometrial stromal sarcomas in p53 (+/-) mice were negative for p21 immunohistochemistry, their counterparts in CBA mice were focally positive at a high incidence, suggesting differences in the processes leading to the tumor development in the two cases.
日本毒性病理学会の論文
2002-12-25