Susceptibility of lean and obese Zucker rats to tumorigenesis induced by N-methyl-N-nitrosourea
Susceptibility of lean and obese Zucker rats to tumorigenesis induced by N-methyl-N-nitrosourea
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DOI：
10.1016/s0304-3835(00)00635-2
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发表时间：
2001-01-26
期刊：
影响因子：
9.7
通讯作者：
Archer, MC
中科院分区：
文献类型：
--
作者：
Lee, WM;Lu, SY;Archer, MC
为了解决高胰岛素血症可能参与乳腺癌的发展，我们研究了瘦和肥胖Zucker大鼠的易感性N-甲基-N-亚硝基脲（MNU）诱导的乳腺癌。50日龄雌性瘦或肥胖Zucker大鼠接受腹膜内（i. p.）注射37.5或20 mg/kg MNU。我们在单独的实验中表明，这些剂量在瘦和肥胖动物的乳腺上皮细胞中产生相似水平的DNA甲基化。在MNU治疗后29周的过程中，一半的瘦大鼠发生乳腺癌，表明它们对乳腺肿瘤发生具有中等易感性。在此期间，肥胖大鼠出现高胰岛素血症和胰岛素抵抗。尽管瘦鼠和肥胖鼠的可触知肿瘤发生率相似，但只有10%的肥胖鼠发生乳腺癌。然而，肥胖的大鼠，主要发生在乳腺区域的表皮囊肿的发病率很高（63.3%）。肥胖大鼠结肠癌发生率为13.3%。这些结果表明，高胰岛素血症的发展并没有使肥胖的Zucker大鼠更容易发生乳腺癌。然而，我们在肥胖大鼠中观察到的结肠癌，而不是瘦大鼠，与高胰岛素血症促进啮齿动物和人类结肠癌的证据一致。(C)2001爱思唯尔科学爱尔兰有限公司版权所有。
To address the possible involvement of hyperinsulinemia in breast cancer development, we have examined the susceptibility of lean and obese Zucker rats to N-methyl-N-nitrosourea (MNU)-induced mammary cancer. Fifty-day-old female lean or obese Zucker rats received intraperitoneal (i.p.) injections of 37.5 or 20 mg/kg MNU, respectively. We showed in separate experiments that these doses produce similar levels of DNA methylation in the mammary epithelial cells of the lean and obese animals. Over the course of 29 weeks following MNU treatment, half of the lean rats developed carcinomas of the mammary gland, demonstrating that they are of intermediate susceptibility to mammary tumorigenesis. During this period, the obese rats developed hyperinsulinemia and insulin resistance as expected. Although palpable tumors developed at a similar rate in the lean and obese rats, only 10% of the obese animals developed mammary carcinomas. The obese rats, however, developed a high incidence (63.3%) of epidermal cysts that occurred mainly in the region of the mammary glands. A 13.3% incidence of colon carcinomas was also found in the obese rats. These results suggest that the development of hyperinsulinemia does not render the obese Zucker rats more susceptible to mammary gland carcinogenesis. Our observation of colon carcinomas in obese, but not lean rats, however, is consistent with evidence that hyperinsulinemia promotes colon cancer in rodents and humans. (C) 2001 Elsevier Science ireland Ltd. All rights reserved.