Increase in incidence of hepatic tumors caused by oncogenic somatic mutation in mice maternally exposed to inorganic arsenic and the multigenerational and transgenerational effects of inorganic arsenic.
Increase in incidence of hepatic tumors caused by oncogenic somatic mutation in mice maternally exposed to inorganic arsenic and the multigenerational and transgenerational effects of inorganic arsenic.
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母体接触无机砷的小鼠致癌体细胞突变导致肝肿瘤发病率增加以及无机砷的多代和跨代效应。
DOI：
--
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kazuyuki Okamura
中科院分区：
文献类型：
--
作者：
K. Nohara;Takehiro Suzuki;Shota Takumi;Kazuyuki Okamura
无机砷是一种天然的环境污染物，已知是人类致癌物。虽然啮齿动物模型在阐明砷的作用模式方面至关重要，但直到最近才很难验证砷在啮齿动物中的致癌性。Waalkes等人（Toxicol Appl Pharmacol 2003; 186：7-17）报告称，母体暴露于亚砷酸盐会增加成年C3 H小鼠雄性幼仔的肝肿瘤发病率。
这一发现表明妊娠期易受砷的影响。使用相同的实验模型，我们发现，母亲砷暴露增加的C61 A Ha-ras基因的体细胞突变引起的肝肿瘤的发病率，该基因编码一种激活的致癌Ha-ras蛋白。G：C到T：A的颠换可归因于氧化应激。我们进一步的研究gpt delta转基因小鼠，这使得在体内突变的检测，和全基因组的DNA甲基化水平的分析，使用甲基化DNA免疫沉淀-CpG岛微阵列方法表明，氧化应激诱导的突变和DNA甲基化的变化参与了在母体暴露于砷的幼崽的肿瘤增大。我们最近的研究还表明，母亲砷暴露增加肝肿瘤的发病率，甚至在孙子（F2代）。在今后的研究中，应考虑母亲接触的多代和跨代影响。
Inorganic arsenic is a natural environmental contaminant and known to be a human carcinogen. Although rodent models are pivotal in elucidating the mode of action of arsenic, it has been difficult to verify the carcinogenicity of arsenic in rodents until recently. Waalkes et al. (Toxicol Appl Pharmacol 2003;
186:7-17) reported that maternal exposure to arsenite increases the incidence of hepatic tumors in the male pups of C3H mice in adulthood. This finding indicated that the gestational period is vulnerable to arsenic. Using the same experimental model, we found that maternal arsenite exposure increases the incidence of hepatic tumors caused by a somatic mutation of the C61A Ha-ras gene, which encodes an activated oncogenic Ha-ras protein. The G:C to T:A transversion is attributable to oxidative stress. Our further studies of gpt delta transgenic mice, which enable detection of in vivo mutation, and genome-wide analysis of DNA methylation levels using the methylated DNA immunoprecipitation-CpG island microarray method suggest that oxidative-stress-induced mutation and DNA methylation changes are involved in the tumor augmentation in the pups maternally exposed to arsenic. Our recent study has also suggested that maternal arsenic exposure increases the incidence of hepatic tumors even in the grandchildren (the F2 generation). Consideration should be given to multigenerational and transgenerational effects of maternal exposure in future studies.
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影响因子：
3.8
作者：
Hughes, Michael F.;Beck, Barbara D.;Thomas, David J.
通讯作者：
Thomas, David J.
影响因子：
3.8
作者：
Waalkes, MP;Ward, JM;Diwan, BA
通讯作者：
Diwan, BA
DOI：
10.1016/j.reprotox.2010.12.055
发表时间：
2011-04
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Perera F;Herbstman J
通讯作者：
Herbstman J
DOI：
10.1073/pnas.0812399106
发表时间：
2009-01-20
影响因子：
11.1
作者：
Rauch, Tibor A.;Wu, Xiwei;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
影响因子：
10.3
作者：
Waalkes, MP;Liu, J;Diwan, BA
通讯作者：
Diwan, BA