Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F2 male offspring via the F1 male offspring

被引:13
作者
Nohara, Keiko [1 ]
Okamura, Kazuyuki [1 ]
Suzuki, Takehiro [1 ]
Murai, Hikari [1 ]
Ito, Takaaki [2 ]
Shinjo, Keiko [3 ]
Takumi, Shota [4 ]
Michikawa, Takehiro [1 ]
Kondo, Yutaka [3 ]
Hata, Kenichiro [5 ]
机构
[1] Natl Inst Environm Studies, Ctr Environm Hlth Sci, Tsukuba, Ibaraki 3058506, Japan
[2] Kumamoto Univ, Grad Sch Med Sci, Dept Pathol & Expt Med, Kumamoto, Japan
[3] Nagoya City Univ, Grad Sch Med, Dept Epigenom, Nagoya, Aichi, Japan
[4] Jikei Univ, Sch Med, Dept Publ Hlth & Environm Med, Tokyo, Japan
[5] Natl Res Inst Child Hlth & Dev, Dept Maternal Fetal Biol, Tokyo, Japan
关键词
arsenic; gestational exposure; hepatic tumor; transgenerational; gene expression; DNA METHYLATION; MUTATION; LIVER; CARCINOGENESIS; INDUCTION; MORTALITY; HUMANS; CANCER;
D O I
10.1002/jat.3149
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:105 / 112
页数:8
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