Radiobiology for Children's Health Program, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Int J Cancer. 2014 Sep 1;135(5):1038-47. doi: 10.1002/ijc.28751. Epub 2014 Feb 11.
Children are especially sensitive to ionizing radiation and chemical carcinogens, and limiting their cancer risk is of great public concern. Calorie restriction (CR) is a potent intervention for suppressing cancer. However, CR is generally not appropriate for children. This study, therefore, examined to see if adult-onset CR influences the lifetime cancer risk in mice after early-life exposure to ionizing radiation. Infant male mice (1-week-old) were exposed to 3.8 Gy X-rays, fed a control 95 kcal/week or CR 65 kcal/week diet from 7 weeks of age (adult stage), and their lifespan and tumor development were assessed. Irrespective of CR, X-rays shortened lifespan by 38%, and irrespective of irradiation CR extended lifespan by 20%. Thymic lymphoma (TL) and early-occurring non-TL were induced by radiation. The liver and Harderian gland were more susceptible to radiation-induced tumors than the lungs and non-thymic lymphoid tissues (late occurring). CR reduced the risk of hepatocellular carcinoma, late-occurring non-TL, lung tumor, Harderian tumor, and hemangioma but had less impact on TL and early-occurring non-TL. Most notably, the effects of X-rays on induction of lung tumors, late-occurring non-TL and hemangioma were essentially canceled by CR. The ability of CR to prevent late-occurring tumors was the same for non-irradiated and irradiated mice, indicating that the mechanism by which CR influences cancer is independent of irradiation. Our results indicate that adult-onset CR significantly inhibits late-occurring tumors in a tissue-dependent manner regardless of infant radiation exposure.
儿童尤其容易受到电离辐射和化学致癌物的影响,限制其癌症风险是公众非常关注的问题。热量限制(CR)是抑制癌症的有效干预措施。然而,CR 一般不适合儿童。因此,本研究旨在观察成年后开始 CR 是否会影响早期暴露于电离辐射的小鼠一生中的癌症风险。雄性幼鼠(1 周龄)接受 3.8 Gy X 射线照射,从 7 周龄(成年期)开始分别给予对照 95 kcal/周或 CR 65 kcal/周饮食,并评估其寿命和肿瘤发展情况。无论是否进行 CR,X 射线都会使寿命缩短 38%,而无论是否照射,CR 都会使寿命延长 20%。X 射线诱导胸腺淋巴瘤(TL)和早期非 TL。肝脏和哈德腺比肺和非胸腺淋巴组织(晚期)更容易受到辐射诱导的肿瘤的影响。CR 降低了肝细胞癌、晚期非 TL、肺肿瘤、哈德腺肿瘤和血管瘤的风险,但对 TL 和早期非 TL 的影响较小。值得注意的是,CR 对诱导肺肿瘤、晚期非 TL 和血管瘤的影响基本上被 X 射线消除了。CR 预防晚期肿瘤的能力对未照射和照射的小鼠是相同的,这表明 CR 影响癌症的机制与照射无关。我们的结果表明,无论婴儿是否接受辐射,成年后开始 CR 都能显著抑制以组织依赖的方式发生的晚期肿瘤。