Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition
Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition
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DOI：
10.1093/carcin/bgi051
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发表时间：
2005-06-01
期刊：
影响因子：
4.7
通讯作者：
Birt, DF
中科院分区：
文献类型：
--
作者：
Stewart, JW;Koehler, K;Birt, DF
我们的实验室在之前的研究中已经证明，饮食能量限制（DER）抑制了皮肤肿瘤发生的促进，其他人发现肾上腺切除术可能逆转这种抑制。本文报道的研究目的是确定循环皮质酮 (CCS) 是否可能是负责 DER 预防皮肤癌发生的肾上腺激素。雌性 SENCAR 小鼠用 7,12-二甲基苯并蒽 (DMBA) 启动，并在假手术或肾上腺切除 (ADX) 小鼠中用 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 进行促进，并随意喂食 (AL) 或能量限制饮食。 DER 占 AL 卡路里摄入量的 60%（除去脂肪和碳水化合物中的能量）。 CCS是小鼠肾上腺分泌的主要糖皮质激素，将其添加到AL/ADX和DER/ADX组的饮用水中，以确定CCS在DER抑制肿瘤发展中的作用。在假手术组中，与 AL 喂养的小鼠相比，DER 小鼠的乳头状瘤发病率和多重性显着降低（P < 0.0001）。 ADX 不会改变 AL 喂养小鼠的乳头状瘤发生率或多重性，但 ADX 部分逆转了 DER 小鼠中乳头状瘤多重性和发生率的抑制。对 DER/ADX 和 AL/ADX 小鼠补充 CCS 可以降低乳头状瘤的发病率和多样性。在 DER/ADX 小鼠中，CCS 显着降低了乳头状瘤发生率，而在 AL/ADX 小鼠中，CCS 将乳头状瘤发生率降低至 DER 假手术组中观察到的水平。与假手术组和 ADX/CCS 组中的 AL 喂养组相比，DER 显着降低了每只有效动物的癌症多样性平均计数 (P < 0.0001)。 DER/ADX 小鼠失去了假手术/DER 小鼠中所见的癌症多重性保护。 ADX 小鼠的 CCS 治疗显着降低了每只有效动物的总癌症（原位和侵袭性）发病率（P < 0.0003）。对 DER 小鼠进行 ADX 治疗后进行 CCS 治疗，癌症发生率和多重性最低。因此，DER 对皮肤肿瘤发生的抑制至少部分是通过 CCS 介导的。然而，CCS 在预防 DER/ADX 小鼠的乳头状瘤和癌方面比 AL/ADX 小鼠更有效，这表明其他因素也可能参与 DER 预防肿瘤形成。
Our laboratory has demonstrated in the previous studies that dietary energy restriction (DER) inhibited the promotion of skin tumorigenesis and others have found that adrenalectomy may reverse that inhibition. The purpose of the research reported here was to determine if circulating corticosterone (CCS) may be the adrenal hormone responsible for DER prevention of skin carcinogenesis. Female SENCAR mice were initiated with 7,12-dimethylbenzanthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) in either sham-operated or adrenalectomized (ADX) mice fed ad libitum (AL) or energy restricted diets. DER was 60% of the AL calorie intake with the removal of energy from fat and carbohydrate. CCS, the main glucocorticoid hormone secreted by the murine adrenal gland, was added to the drinking water of AL/ADX and DER/ADX groups to determine the role of CCS in the DER inhibition of tumor development. In sham-operated groups, DER compared with AL-fed mice experienced significantly decreased papilloma incidence and multiplicity (P < 0.0001). ADX did not alter papilloma incidence or multiplicity in AL-fed mice but ADX partially reversed the inhibition of papilloma multiplicity and incidence in DER mice. CCS supplementation to both DER/ADX and AL/ADX mice resulted in reduced papilloma incidence and multiplicity. In DER/ADX mice, CCS dramatically reduced papilloma rates while in AL/ADX mice CCS reduced the papilloma rates to those seen in the DER sham group. DER significantly reduced carcinoma multiplicity mean counts per effective animal (P < 0.0001) compared with AL-fed groups in sham and ADX/CCS groups. DER/ADX mice lost the carcinoma multiplicity protection seen in sham/DER mice. CCS treatment of ADX mice significantly decreased total carcinoma (in situ and invasive) incidence rates per effective animal (P < 0.0003). ADX followed by CCS treatment in the DER mice resulted in the lowest carcinoma incidence and multiplicity. Thus, DER-inhibition of skin tumorigenesis was mediated at least in part through CCS. However, CCS was more effective in preventing papillomas and carcinomas in DER/ADX mice than in AL/ADX mice, suggesting that other factors may also be involved in the DER prevention of tumor formation.