Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F2 male offspring via the F1 male offspring
Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F2 male offspring via the F1 male offspring
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DOI：
10.1002/jat.3149
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Hata, Kenichiro
中科院分区：
文献类型：
--
作者：
Nohara, Keiko;Okamura, Kazuyuki;Hata, Kenichiro
妊娠期暴露可通过暴露F-1生殖细胞而影响F-2代。以前的研究报道，在怀孕期间只接触F-0雌性的亚砷酸盐会增加C3H小鼠F-1雄性的肝脏肿瘤，这些雄性小鼠在以后的生活中更容易自发地患上肝脏肿瘤。本研究探讨了孕期亚砷酸盐暴露对C3H小鼠F-2雄鼠肿瘤发生的影响。对53周龄和80周龄正常肝脏中几个基因的表达分析清楚地表明，与对照F-2雄鼠相比，孕期接触亚砷酸盐的F-1雄鼠和雌性F-2雄鼠获得的F-2雄鼠发生了显著变化。其中一些变化被证明是以迟发的方式发生的。然后，通过对照和亚砷酸盐-F-1雌雄正反杂交获得的F-2雄鼠，在75-82周龄时评估肿瘤发病率。结果表明，亚砷酸盐-F-1雄鼠所生的F-2雄鼠的肿瘤发生率显著高于对照F-1雄鼠所生的F-2雄鼠，而与F-1雌鼠的暴露无关。亚砷酸盐-F-1雄鼠所生的F-2与对照F-1雄鼠相比，肝癌标志物-连环素(CTNNB1)和白介素1受体拮抗剂在肿瘤中的基因表达显著上调。这些结果表明，只有F-0孕鼠接触亚砷酸盐会引起迟发性变化，并通过影响F-1雄鼠后代而增加F-2雄鼠的肝脏肿瘤。版权所有(C)2015 John Wiley&Sons，Ltd.妊娠期暴露可通过暴露F-1生殖细胞影响F-2代。我们评估了通过对照和孕期接触亚砷酸盐的F-1雄鼠和雌鼠的正反交获得的F-2雄鼠的肿瘤发病率。结果表明，亚砷酸盐-F-1雄鼠所生的F-2雄鼠的肿瘤发生率显著高于对照F-1雄鼠所生的F-2雄鼠。我们还研究了几种肝细胞癌标记物在F-2肿瘤中的基因表达。
Gestational exposure can affect the F-2 generation through exposure of F-1 germline cells. Previous studies reported that arsenite exposure of only F-0 females during their pregnancy increases hepatic tumors in the F-1 males in C3H mice, whose males are predisposed spontaneously to develop hepatic tumors later in life. The present study addressed the effects of gestational arsenite exposure on tumorigenesis of the F-2 males in C3H mice. Expression analysis of several genes in the normal livers at 53 and 80weeks of age clearly showed significant changes in the F-2 males obtained by crossing gestational arsenite-exposed F-1 (arsenite-F-1) males and females compared to the control F-2 males. Some of the changes were shown to occur in a late-onset manner. Then the tumor incidence was assessed at 75-82 weeks of age in the F-2 males obtained by reciprocal crossing between the control and arsenite-F-1 males and females. The results demonstrated that the F-2 males born to arsenite-F-1 males developed tumors at a significantly higher rate than the F-2 males born to the control F-1 males, irrespective of exposure of F-1 females. Gene expressions of hepatocellular carcinoma markers -catenin (CTNNB1) and interleukin-1 receptor antagonist in the tumors were significantly upregulated in the F-2 males born to arsenite-F-1 males compared to those born to the control F-1 males. These results show that arsenite exposure of only F-0 pregnant mice causes late-onset changes and augments tumors in the livers of the F-2 males by affecting the F-1 male offspring. Copyright (c) 2015 John Wiley & Sons, Ltd.Gestational exposure can affect the F-2 generation through exposure of F-1 germ cells. We assessed tumor incidence in the F-2 males obtained by reciprocal crossing between the control and gestationally arsenite-exposed F-1 males and females in C3H mice. The results demonstrated that the F-2 males born to arsenite-F-1 males developed tumors at a significantly higher rate than the F-2 males born to the control F-1 males. We also characterized gene expression of several hepatocellular carcinoma markers in the F-2 tumors.