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While people who eat a lot of red meat are known to be at higher risk for certain cancers, other carnivores are not, prompting researchers at the University of California, San Diego School of Medicine to investigate the possible tumor-forming role of a sugar called Neu5Gc, which is naturally found in most mammals but not in humans.
In a study published in the Dec. 29 online early edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers. The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer.
"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. "This is the first time we have directly shown that mimicking the exact situation in humans -- feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies -- increases spontaneous cancers in mice."
Varki's team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin such as these are the primary sources of Neu5Gc in the human diet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.
The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.
To test this hypothesis, the team engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.
"The final proof in humans will be much harder to come by," Varki said. "But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.
"Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22."
参考译文：
长期以来，大量可重复的流行病学资料显示，人类长期食用哺乳动物源“红肉”（牛肉、猪肉和羊肉等）增加癌症发生风险。虽然，迄今已经有多种理论被提出试图用来解释这种现象，但是都没有被最终证实。
12月29日发表在美国国家科学院院刊网络版上的一项研究中，科学家发现，给经过基因工程改造象人类一样存在Neu5Gc缺陷的小鼠喂食非人类唾液酸N-羟乙酰神经氨酸（Neu5Gc）显著促进癌症发生。该研究中由于实验小鼠没有涉及致癌物质暴露或人工诱导肿瘤，进一步提示Neu5Gc可能是红肉消费和癌症之间关联的一个关键因素。
加州大学圣迭戈穆尔斯癌症研究中心首席研究员阿吉特•瓦尔基博士领导的研究团队首先对人类常见食物系统进行筛查。他们发现，哺乳动物源性红肉含有丰富的Neu5Gc，而这种糖分子物质容易被人体吸收，口服后生物利用度高，可以通过血液分布到整个身体组织。
因此，研究人员推测，由于人类缺乏Neu5Gc，那么被人踢吸收后可能坐位一种外源性抗原激发人体免疫反应而引发炎症反应。而慢性炎症是已知的一种致癌因素。
为了验证这一假设，研究团队利用基因工程技术改造出模拟人体的Neu5Gc缺陷小鼠。由于这些小鼠缺乏Neu5Gc，喂食它们Neu5Gc后激发了全身炎症反应，自发性肿瘤的发生增加了五倍，而且肿瘤组织内富集Neu5Gc存在。
“虽然难以在人类获得最终的证实，但是在更广泛的意义上，这项工作也有助于解释红肉消费与其他可以由慢性炎症加重的其他疾病，如动脉粥样硬化和2型糖尿病等之间潜在的联系。”瓦尔基博士说。
原始来源：http://www.sciencedaily.com/releases/2014/12/141229152226.htm
In a study published in the Dec. 29 online early edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers. The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer.
"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. "This is the first time we have directly shown that mimicking the exact situation in humans -- feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies -- increases spontaneous cancers in mice."
Varki's team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin such as these are the primary sources of Neu5Gc in the human diet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.
The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.
To test this hypothesis, the team engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.
"The final proof in humans will be much harder to come by," Varki said. "But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.
"Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22."
参考译文：
长期以来，大量可重复的流行病学资料显示，人类长期食用哺乳动物源“红肉”（牛肉、猪肉和羊肉等）增加癌症发生风险。虽然，迄今已经有多种理论被提出试图用来解释这种现象，但是都没有被最终证实。
12月29日发表在美国国家科学院院刊网络版上的一项研究中，科学家发现，给经过基因工程改造象人类一样存在Neu5Gc缺陷的小鼠喂食非人类唾液酸N-羟乙酰神经氨酸（Neu5Gc）显著促进癌症发生。该研究中由于实验小鼠没有涉及致癌物质暴露或人工诱导肿瘤，进一步提示Neu5Gc可能是红肉消费和癌症之间关联的一个关键因素。
加州大学圣迭戈穆尔斯癌症研究中心首席研究员阿吉特•瓦尔基博士领导的研究团队首先对人类常见食物系统进行筛查。他们发现，哺乳动物源性红肉含有丰富的Neu5Gc，而这种糖分子物质容易被人体吸收，口服后生物利用度高，可以通过血液分布到整个身体组织。
因此，研究人员推测，由于人类缺乏Neu5Gc，那么被人踢吸收后可能坐位一种外源性抗原激发人体免疫反应而引发炎症反应。而慢性炎症是已知的一种致癌因素。
为了验证这一假设，研究团队利用基因工程技术改造出模拟人体的Neu5Gc缺陷小鼠。由于这些小鼠缺乏Neu5Gc，喂食它们Neu5Gc后激发了全身炎症反应，自发性肿瘤的发生增加了五倍，而且肿瘤组织内富集Neu5Gc存在。
“虽然难以在人类获得最终的证实，但是在更广泛的意义上，这项工作也有助于解释红肉消费与其他可以由慢性炎症加重的其他疾病，如动脉粥样硬化和2型糖尿病等之间潜在的联系。”瓦尔基博士说。
原始来源：http://www.sciencedaily.com/releases/2014/12/141229152226.htm
