Hajek R A, Nguyen T V, Johnston D A, Jones L A
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Biol Reprod. 1993 Nov;49(5):908-17. doi: 10.1095/biolreprod49.5.908.
The purpose of this study was to test the hypothesis that exposure to natural estrogen early in the development of hormone-dependent tissue induces a change in nuclear DNA content. Female BALB/c mice were treated neonatally with daily s.c. injections of either 25 micrograms of 17 beta-estradiol (E2) in 0.02 ml of sesame oil (vehicle) or vehicle alone for 5 days. Treatment was begun either within 15 h of birth or 6 days after birth. One set each of 10-day-old E2-treated and control mice received s.c. pellet implants containing 15 mg of E2 and cholesterol (10% E2 and 90% cholesterol), a second set received implants containing 25 mg of cholesterol alone, and a third set did not receive implants. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 21, 40, 70, 180, or 240 days of age. The results obtained include several important findings: 1) neonatal E2 treatment in BALB/c mice causes an increase in nuclear DNA content in cervicovaginal epithelium; 2) short-term administration of secondary exogenous E2 reduces the latency period for the appearance of increased nuclear DNA content in neonatally E2-treated cervicovaginal epithelium; 3) increased nuclear DNA content can indicate abnormal cervicovaginal epithelium before histological abnormalities become evident; and 4) there is a sensitive period for neonatal E2 induction of increased nuclear DNA content in the cervicovaginal epithelium. These findings support other reports of the carcinogenic potential of estrogen in vivo. Therefore, increased DNA ploidy may be an important early detectable event in estrogen-induced carcinogenesis.
在激素依赖性组织发育早期接触天然雌激素会导致核DNA含量发生变化。雌性BALB/c小鼠在出生后接受皮下注射，连续5天每天注射0.02 ml芝麻油（载体）中含有的25微克17β-雌二醇（E2）或仅注射载体。治疗在出生后15小时内或出生后6天开始。每组10只10日龄经E2处理的小鼠和对照小鼠，一组接受皮下植入含15 mg E2和胆固醇（10% E2和90%胆固醇）的小球，第二组接受仅含25 mg胆固醇的植入物，第三组不接受植入物。在21、40、70、180或240日龄时，对完整BALB/c小鼠的宫颈阴道组织进行组织学检查和流式细胞术分析。获得的结果包括几个重要发现：1）BALB/c小鼠出生后接受E2治疗会导致宫颈阴道上皮细胞核DNA含量增加；2）短期给予二次外源性E2可缩短出生后接受E2治疗的宫颈阴道上皮细胞核DNA含量增加出现的潜伏期；3）在组织学异常明显之前，核DNA含量增加可表明宫颈阴道上皮异常；4）出生后E2诱导宫颈阴道上皮细胞核DNA含量增加存在敏感期。这些发现支持了雌激素在体内致癌潜力的其他报道。因此，DNA倍体增加可能是雌激素诱导致癌过程中一个重要的早期可检测事件。
