Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats.
Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats.
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肥胖可促进雌性扎克大鼠蒽诱导的乳腺肿瘤发育的7,12-二甲基苯子。
DOI：
10.1186/bcr1263
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Korourian S
中科院分区：
文献类型：
--
作者：
Hakkak R;Holley AW;Macleod SL;Simpson PM;Fuchs GJ;Jo CH;Kieber-Emmons T;Korourian S
高体重指数与患各种癌症的风险增加有关，包括乳腺癌。本文描述了使用7,12-二甲基苯(a)蒽（DMBA）研究肥胖在DMBA诱导的雌性Zucker大鼠（fa/fa）乳腺肿瘤易感性中的作用，这是最广泛使用的遗传性肥胖大鼠模型。50日龄雌性肥胖（n = 25）和瘦弱（n = 28） Zucker大鼠灌胃65 mg/kg DMBA。每周两次对大鼠进行称重和触诊以检测乳腺肿瘤。DMBA治疗后139天处死大鼠。肥胖组在DMBA治疗后49天发现第一个乳腺肿瘤，而瘦组在治疗后86天发现第一个乳腺肿瘤（P < 0.001）。肥胖组中位无瘤时间显著低于肥胖组（P < 0.001）。用DMBA治疗后25%的大鼠发生乳腺肿瘤的天数作为肿瘤潜伏期的标志，肥胖组的潜伏期（66天）明显短于瘦组（118天）。在研究结束时，与瘦鼠组相比，肥胖大鼠的乳腺肿瘤发病率明显（P < 0.001）更高（68%对32%）。乳腺肿瘤组织学检查结果显示，与瘦鼠相比，肥胖大鼠至少有一种浸润性导管癌和小叶癌的数量显著增加（P < 0.05）。我们的研究结果表明，肥胖增加了雌性Zucker大鼠对dmba诱导的乳腺肿瘤的易感性，进一步支持了肥胖及其部分介质在致癌过程中发挥重要作用的假设。
High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.
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