Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Free Radic Res. 2011 Aug;45(8):906-17. doi: 10.3109/10715762.2011.564170. Epub 2011 May 26.
Iron is universally abundant and no life can exist without it. However, iron levels should be maintained within a narrow range. Iron deficiency causes anaemia, whereas excessive iron increases cancer risk, presumably by free radical generation. Several pathological conditions such as genetic haemochromatosis, chronic viral hepatitis B and C, conditions related to asbestos fibre exposure and ovarian endometriosis have been recognized as iron overload-associated conditions that also increase human cancer risks. Iron's carcinogenicity has been documented in animal experiments. Surprisingly, these studies have revealed that the homozygous deletion of CDKN2A/2B is a major hallmark of iron-induced carcinogenesis. Recently, the hormonal regulation of iron metabolism has been elucidated. A commonly hypothesized mechanism may be the lack of any iron disposal pathway other than for bleeding and a mechanism of iron re-uptake as catechol chelate has been discovered. Iron overload in neurons via the ferroportin block may play a role in Alzheimer's disease. Furthermore, a recent epidemiological study reported that iron reduction by phlebotomy was associated with decreased cancer risks in a general population. Given that the required amounts of iron decrease during ageing, the fine control of body iron stores would be a wise strategy for chemoprevention of several diseases.
铁在自然界中广泛存在,没有它任何生命都无法生存。然而,铁的含量应该保持在一个狭窄的范围内。缺铁会导致贫血,而过量的铁会增加癌症的风险,这可能是通过自由基的产生。一些病理状况,如遗传性血色素沉着症、慢性乙型和丙型肝炎、与石棉纤维暴露和卵巢子宫内膜异位症相关的状况,已被认为是与铁过载相关的状况,也会增加人类癌症的风险。铁的致癌性在动物实验中得到了证实。令人惊讶的是,这些研究表明,CDKN2A/2B 的纯合缺失是铁诱导致癌的主要标志。最近,铁代谢的激素调节已经阐明。一种常见的假设机制可能是除了出血之外没有其他铁处理途径,并且发现了一种铁再摄取的机制,即儿茶酚螯合物。通过铁蛋白阻断使神经元中铁过载可能在阿尔茨海默病中起作用。此外,最近的一项流行病学研究报告称,放血减少铁含量与普通人群癌症风险降低有关。鉴于衰老过程中铁的需求量减少,精细控制体内铁储存将是预防多种疾病的明智策略。
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