Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F sub(2) male offspring via the F sub(1) male offspring

Gestational exposure can affect the F sub(2) generation through exposure of F sub(1) germline cells. Previous studies reported that arsenite exposure of only F sub(0) females during their pregnancy increases hepatic tumors in the F sub(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 sub(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 sub(2) males obtained by crossing gestational arsenite-exposed F sub(1) (arsenite-F sub(1)) males and females compared to the control F sub(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 sub(2) males obtained by reciprocal crossing between the control and arsenite-F sub(1) males and females. The results demonstrated that the F sub(2) males born to arsenite-F sub(1) males developed tumors at a significantly higher rate than the F sub(2) males born to the control F sub(1) males, irrespective of exposure of F sub(1) females. Gene expressions of hepatocellular carcinoma markers beta -catenin (CTNNB1) and interleukin-1 receptor antagonist in the tumors were significantly upregulated in the F sub(2) males born to arsenite-F sub(1) males compared to those born to the control F sub(1) males. These results show that arsenite exposure of only F sub(0) pregnant mice causes late-onset changes and augments tumors in the livers of the F sub(2) males by affecting the F sub(1) male offspring. Gestational exposure can affect the F sub(2) generation through exposure of F sub(1) germ cells. We assessed tumor incidence in the F sub(2) males obtained by reciprocal crossing between the control and gestationally arsenite-exposed F sub(1) males and females in C3H mice. The results demonstrated that the F sub(2) males born to arsenite-F sub(1) males developed tumors at a significantly higher rate than the F sub(2) males born to the control F sub(1) males. We also characterized gene expression of several hepatocellular carcinoma markers in the F sub(2) tumors.