Rao G N, Ney E, Herbert R A
Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Breast Cancer Res Treat. 2000 Dec;64(3):287-96. doi: 10.1023/a:1026552405042.
Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of a MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05-0.2 ml of flaxseed oil as the source of omega-3 rich PUFA, or melatonin at 50-200 mg/kg or a combination of 0.10 ml flaxseed oil and 50 mg/kg melatonin in a gavage volume of 0.2 ml per mouse with corn oil as the vehicle for 30 weeks. The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control. At the high dose (0.2 ml) of flaxseed oil, when the omega-6: omega-3 PUFA ratio was closer to 1, there was some delay in the growth of mammary tumors. Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors. The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone. Flaxseed oil may delay the growth of mammary tumors if the omega-6:omega-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.
乳腺癌是最常见的癌症之一，也是女性死亡的主要原因。TG.NK转基因小鼠品系在MMTV启动子的控制下表达c-neu乳腺癌致癌基因，似乎是评估延迟/预防乳腺癌干预策略的有用动物模型。富含纤维的非纯化饮食（NTP-2000）和一些类视黄醇类似物已被证明能显著延缓TG.NK模型中乳腺癌的发展。给四周龄携带MMTV/c-neu致癌基因的半合子TG.NK雌性小鼠喂食NTP-2000饮食，以0.05 - 0.2毫升亚麻籽油作为富含ω-3多不饱和脂肪酸的来源，或以50 - 200毫克/千克的褪黑素，或以0.10毫升亚麻籽油和50毫克/千克褪黑素的组合进行灌胃，每只小鼠的灌胃体积为0.2毫升，以玉米油作为载体，持续30周。与对照组相比，亚麻籽油使乳腺肿瘤发生率模式的时间进程提前。在高剂量（0.2毫升）亚麻籽油时，当ω-6:ω-3多不饱和脂肪酸比例更接近1时，乳腺肿瘤的生长有一定延迟。褪黑素延迟了可触及肿瘤的出现以及肿瘤的生长，肿瘤发生率呈剂量相关的统计学显著负趋势。与对照组和亚麻籽油单独使用相比，亚麻籽油和褪黑素的组合使每只小鼠的肿瘤数量和肿瘤重量显著减少，但与单独使用褪黑素相比无此效果。如果所摄入脂肪的ω-6:ω-3多不饱和脂肪酸比例更接近1，亚麻籽油可能会延缓乳腺肿瘤的生长。褪黑素有可能显著延迟可触及乳腺肿瘤的出现。目前正在利用TG.NK小鼠模型进行研究，以了解在使用广泛剂量的褪黑素治疗后，与乳腺肿瘤发生率和生长的剂量反应模式相关的组织学和分子变化。
