Christov K, Swanson S M, Guzman R C, Thordarson G, Jin E, Talamantes F, Nandi S
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Carcinogenesis. 1993 Oct;14(10):2019-25. doi: 10.1093/carcin/14.10.2019.
Recently, we have published that treatment of pituitary isografted BALB/c mice with a single injection of N-methyl-N-nitrosourea (MNU) leads to the rapid development of mammary tumors in over 90% of the animals (Guzman et al., Cancer Res., 52, 5732-5737). In the present study, we characterized the changes in proliferative activity and lobulo-alveolar differentiation of MECs at different time intervals after isografting animals with pituitary glands. Virgin BALB/c mice 1, 3, 5 or 8 weeks after pituitary isografting were either pulse-labeled for 2 h or continuously infused with bromodeoxyuridine (BrdU) and the percentage of BrdU-labeled MECs was assessed. The S-phase duration (TS) of MECs was evaluated by double labeling with [3H]thymidine and BrdU. The population potential doubling time (TP) was calculated from the values of BrdU-LI and TS. Three stages of proliferation and differentiation of MECs in pituitary isografted virgin BALB/c mice were observed: (i) A sharp increase in the percentage of proliferating MECs of the terminal ducts and ductal branchings in the first 1-2 weeks, (ii) Development of lobulo-alveolar structures from the terminal ductal and alveolar buds, between weeks 3 and 5 with the highest BrdU-LI in week 3 and (iii) Multiplication of the alveolar structures and decrease in the BrdU-LI between weeks 5 and 8. The BrdU-LIs of alveolar cells 5 weeks after isografting the animals were significantly higher than those of the ductal cells. The continuous administration of BrdU for 3, 5 or 7 days by using osmotic pumps revealed zones in the ducts where almost all MECs were labeled as well as zones lacking proliferate activity. When the BrdU administration was extended for 10-14 days, almost all (> 95%) ductal and lobular epithelial cells were labeled. A small percentage (< 5%), of ductal and lobulo-alveolar MECs cells, remained unlabeled even after 14 days infusion of BrdU. The TS and TP values were shorter in pituitary isografted animals than in controls, but no significant difference was found for either values between the ductal and alveolar cells in either isografted or control mice. Changes in proliferation kinetics of mouse MECs in pituitary isografted animals correlated with the circulating concentrations of prolactin, progesterone and 17 beta-estradiol, but not with corticosterone, growth hormone or thyroxin.(ABSTRACT TRUNCATED AT 400 WORDS)
最近，我们发表了一项研究，即对垂体同基因移植的BALB/c小鼠单次注射N-甲基-N-亚硝基脲（MNU），会导致超过90%的动物快速发生乳腺肿瘤（古兹曼等人，《癌症研究》，52卷，5732 - 5737页）。在本研究中，我们对垂体移植动物在不同时间间隔后乳腺上皮细胞（MECs）的增殖活性变化和小叶 - 腺泡分化进行了表征。垂体移植后1、3、5或8周的未孕BALB/c小鼠，要么进行2小时的脉冲标记，要么持续注入溴脱氧尿苷（BrdU），并评估BrdU标记的MECs百分比。通过用[³H]胸腺嘧啶核苷和BrdU进行双重标记来评估MECs的S期持续时间（TS）。根据BrdU标记指数（LI）和TS值计算群体潜在倍增时间（TP）。观察到垂体同基因移植的未孕BALB/c小鼠中MECs增殖和分化的三个阶段：（i）在最初1 - 2周内，终末导管和导管分支中增殖的MECs百分比急剧增加；（ii）在第3至5周期间，从终末导管和腺泡芽发育出小叶 - 腺泡结构，第3周时BrdU - LI最高；（iii）在第5至8周期间，腺泡结构增殖且BrdU - LI降低。移植动物5周后，腺泡细胞的BrdU - LI显著高于导管细胞。使用渗透泵连续3、5或7天给予BrdU，发现导管中有几乎所有MECs都被标记的区域以及缺乏增殖活性的区域。当BrdU给药延长至10 - 14天时，几乎所有（> 95%）的导管和小叶上皮细胞都被标记。即使在注入BrdU 14天后，仍有一小部分（< 5%）的导管和小叶 - 腺泡MECs细胞未被标记。垂体移植动物中MECs的TS和TP值比对照组短，但在移植或对照小鼠中，导管和腺泡细胞之间的这两个值均未发现显著差异。垂体移植动物中小鼠MECs增殖动力学的变化与催乳素、孕酮和17β - 雌二醇的循环浓度相关，但与皮质酮、生长激素或甲状腺素无关。（摘要截断于400字）
