LIGHT DURING DARKNESS AND BREAST CANCER PROGRESSION

描述(申请人提供)：本研究的长期目标是 确定黑暗中的光线是否是乳腺癌的风险因素 进步。工业化国家的人们正在接触到更多 夜间有人工照明，乳腺癌的发病率也在增加。 松果体激素褪黑激素，抑制实验性人类乳房 癌症生长，是在黑暗中产生的；光在黑暗中出现 抑制褪黑激素的合成。要检验的假设是：光，光， 适当的强度、持续时间、时间和波长，在 黑暗，通过抑制褪黑激素和一种 由此解除对肿瘤亚油酸(LA)摄取和代谢的抑制。这个 第一个目标是测量裸体女性暴露的剂量反应效应。 大鼠，携带组织分离的雌激素受体(ER)和孕激素受体 (PGR)MCF-7人乳腺癌移植瘤，不同强度的白色 黑暗中的光线，褪黑素抑制与肿瘤生长的关系，LA 代谢与相关生长信号转导分子的表达 (即ER和PGR、褪黑素受体和cAMP)。第二个目标是确定 裸鼠MCF-7裸鼠移植瘤的剂量-反应效应 与ER/PGR-MDA-MB-231人乳腺癌的比较 不同白光强度异种移植对小鼠褪黑素的抑制作用 与肿瘤生长的关系。第三个目标是确定褪黑激素 更换将防止白光照射的刺激效应 黑暗对肿瘤生长、LA代谢及相关基因表达的影响 肿瘤生长信号转导分子。第四个目标将考验 黑暗中光照时间和时间对肿瘤的影响 生长和生长信号转导事件。这项研究可能会导致 阐明“夜间灯光”与膳食脂肪摄入量是一种新的 乳腺癌进展的危险因素及新的预防措施 通过结合室内照明的改进来降低乳腺癌风险 和补充褪黑激素的膳食脂肪摄入量。

DESCRIPTION (provided by applicant): The long-term goal of this research is to determine if light, present during darkness, is a risk factor for breast cancer progression. People in industrialized nations are being exposed to more artificial light during the night and the rate of breast cancer is increasing. The pineal gland hormone melatonin, which inhibits experimental human breast cancer growth, is produced during darkness; light present during darkness suppresses melatonin synthesis. The hypothesis to be tested is: Light, of the appropriate intensity, duration, timing and wavelength, present during darkness, stimulates breast cancer progression via melatonin suppression and a resultant disinhibition of tumor linoleic acid (LA) uptake and metabolism. The first aim is to measure the dose-response effects of exposure of nude female rats, bearing tissue-isolated estrogen receptor (ER)+ and progesterone receptor (PgR)+ MCF-7 human breast cancer xenografts, to different intensities of white light during darkness, on melatonin suppression in relation to tumor growth, LA metabolism and the expression of related growth signal transduction molecules (i.e., ER and PgR, melatonin receptor and cAMP). The second aim is to determine the dose-response effects of exposure of nude rats bearing MCF-7 xenografis in comparison with those bearing ER/PgR- MDA-MB-23 1 human breast cancer xenografts to different intensities of white light on melatonin suppression in relation to tumor growth. The third aim is to determine whether melatonin replacement will prevent the stimulative of effects of white light exposure during darkness on tumor growth, LA metabolism and the expression of related tumor growth signal transduction molecules. The fourth aim will test the effects of the duration and timing of light exposure during darkness on tumor growth and growth signal transduction events. This research may lead to the elucidation of "light-at-night" in conjunction with dietary fat intake as a new risk factor for breast cancer progression and to novel preventative measures for lowering breast cancer risk by combining modifications of indoor lighting and dietary fat intake with melatonin supplementation.