Superiority of rat over murine model for studies on the evolution of cancer genome
Superiority of rat over murine model for studies on the evolution of cancer genome
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DOI：
10.1080/10715762.2018.1467562
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发表时间：
2018-12-02
影响因子：
3.3
通讯作者：
Toyokuni, Shinya
中科院分区：
文献类型：
--
作者：
Akatsuka, Shinya;Li, Guang Hua;Toyokuni, Shinya
物种的进化和致癌作用是相似的，因为基因组改变是关键事件。各种病因引起的氧化应激是通过诱导基因组突变而致癌的主要原因之一。氮基三乙酸铁（Fe-NTA）催化的芬顿反应导致小鼠和大鼠肾近曲小管持续氧化应激，导致肾细胞癌（RCC）的发生。在这里，为了观察氧化应激诱导的致癌作用的物种差异，并获得关于每个物种的特征的见解，我们使用基于阵列的比较基因组杂交在Mutyh敲除/野生型小鼠中的RCC之间比较基因组改变（C57 BL/6背景），Brown-Norway/Fischer-344野生型大鼠的F1杂种和人的透明细胞肾细胞癌（CCRCC）/乳头状肾细胞癌（PRCC）中的RCC。对于鼠RCC、大鼠RCC、人CCRCC和人PRCC，基因组区段的平均偏离分数（丢失或获得）分别为0.220（N = 4）、0.304（N = 11）、0.283（N = 12）和0.261（N = 5）。值得注意的是，增益/损失比显著不同，分别为0.0820、0.161、0.821和4.44。这些数据表明，更高的物种需要更多的基因组变异与扩增偏好肾癌。目前的研究结果是否取决于细胞功能差异、致癌原因或致癌过程中的靶细胞，还需要进一步的研究来确定其分子机制。
Evolution of the species and carcinogenesis are similar in that genomic alterations are the key events. Oxidative stress derived from various etiologies is one of the major causes of carcinogenesis by inducing mutations in the genome. Persistent oxidative stress in the renal proximal tubules through Fenton reaction catalysed by ferric nitrilotriacetate (Fe-NTA) generates renal cell carcinoma (RCC) in mice and rats. Here, in order to observe the species difference in oxidative stress-induced carcinogenesis and to obtain an insight regarding the characteristics of each species, we compared the genomic alterations using array-based comparative genome hybridisation among RCCs in Mutyh knockout/wild-type mice (C57BL/6 background) induced by Fe-NTA, RCCs in F1 hybrids of Brown-Norway/Fischer-344 wild-type rats and clear cell renal cell carcinoma (CCRCC)/papillary renal cell carcinoma (PRCC) of humans. The average deviated fraction of genomic segments, either loss or gain, from the standard biallelic position was 0.220 (N = 4), 0.304 (N = 11), 0.283 (N = 12), and 0.261 (N = 5), respectively, for murine RCC, rat RCC, human CCRCC, and human PRCC. Notably, gain/loss ratio was remarkably different as indicated by 0.0820, 0.161, 0.821, and 4.44, respectively. These data suggest that higher species require more genomic alterations with amplification preference for renal carcinogenesis. Further studies are necessary to identify the molecular mechanisms whether the present results depend on cellular functional differences, etiology of carcinogenesis or the target cells in carcinogenesis.