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

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.