Here, we demonstrate that the short-term, but not the long-term, SAM supplementation to FVB/N Mdr2-KO mice starting at the late precancerous stage, significantly decreased the numbers of small tumor nodules, of proliferating and polyploid (binuclear) hepatocytes, and the total DNA methylation level, while it increased the expression of the Mat1a, p21/Cdkn1a and γH2AX proteins in the livers of treated Mdr2-KO mice. Here, ABCB4 is linked to neoplasm.