Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
In Vivo. 2010 Jul-Aug;24(4):553-60.
Short-term oestrogen and progesterone treatment (STEPT) mimics the pregnancy hormone milieu. This study compared the development of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Lewis rats that received STEPT in early or later life.
Rats in Groups 1 and 2 received a single intraperitoneal injection of 50 mg/kg MNU at 4 weeks old. Pellets containing 0.5 mg 17beta-estradiol and 32.5 mg progesterone (EP) were subcutaneously implanted in rats in Group 1 during 6-9 weeks old. Rats in Groups 3 and 4 received 50 mg/kg MNU at 22 weeks old and again at 23 weeks old. EP pellets were implanted in rats in Group 3 during 24-27 weeks old. At the time of EP removal and 8 weeks afterward, 4 randomly selected rats in each group were sacrificed for blood sampling. The fatty acid composition of serum phospholipids was measured by capillary gas chromatography. The remaining rats were sacrificed when they developed mammary tumours >or=1 cm in diameter or at the termination of the experiment, which was at 18 weeks old for Groups 1 and 2 and at 64 weeks old for Groups 3 and 4. Mammary cancer was histologically confirmed.
Group 1 had a significantly suppressed incidence of mammary cancer compared to Group 2 (7% vs. 90%), whereas the cancer incidence in Group 3 was similar to that of Group 4 (50% vs. 56%). Rats in Group 1 had significantly smaller n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and higher levels of docosahexaenoic acid (DHA) than those in Group 2 at the time of EP removal but not 8 weeks after EP removal. Neither the PUFA ratios nor the DHA levels differed between Groups 3 and 4 at any time. These data suggest that the age at which STEPT is administered is important, since its mammary cancer-suppressing potential was lost in aged animals.
DHA and the n-6/n-3 PUFA ratio may play a crucial role in mammary cancer suppression by STEPT.
短期雌激素和孕激素治疗（STEPT）模拟妊娠激素环境。本研究比较了接受早期或晚期 STEPT 的雌性 Lewis 大鼠中 N-甲基-N-亚硝脲（MNU）诱导的乳腺癌的发展。
第 1 组和第 2 组大鼠在 4 周龄时接受单次腹腔注射 50mg/kg MNU。第 1 组大鼠在 6-9 周龄时皮下植入含有 0.5mg 17β-雌二醇和 32.5mg 孕酮（EP）的丸剂。第 3 组和第 4 组大鼠在 22 周龄和 23 周龄时再次接受 50mg/kg MNU。第 3 组大鼠在 24-27 周龄时植入 EP 丸剂。在 EP 去除和 8 周后，每组随机选择 4 只大鼠处死采血。通过毛细管气相色谱法测量血清磷脂的脂肪酸组成。当大鼠出现>或=1cm 直径的乳腺肿瘤或实验结束时（第 1 组和第 2 组为 18 周龄，第 3 组和第 4 组为 64 周龄），其余大鼠被处死。通过组织学确认乳腺癌。
与第 2 组相比，第 1 组的乳腺癌发病率显著降低（7%对 90%），而第 3 组的癌症发病率与第 4 组相似（50%对 56%）。在 EP 去除时，第 1 组大鼠的 n-6/n-3 多不饱和脂肪酸（PUFA）比值显著低于第 2 组，二十二碳六烯酸（DHA）水平显著高于第 2 组，但在 EP 去除 8 周后无差异。第 3 组和第 4 组在任何时候的 PUFA 比值和 DHA 水平均无差异。这些数据表明，STEPT 的给药年龄很重要，因为其乳腺癌抑制作用在老年动物中丧失。
DHA 和 n-6/n-3 PUFA 比值可能在 STEPT 抑制乳腺癌中发挥关键作用。
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