Marked increase of micronuclei in K243R/+ mice. (A) The frequency of MEFs that display lagging chromosomes (WT, n = 52; K243R/+, n = 153). (B) The frequency of micronuclei shown in bar graphs (WT, n = 52; K243R/+, n = 1,976). (C) γ-H2AX–positive micronuclei (arrows) in K243R/+ MEFs. The cells were stained with a γ-H2AX antibody, and DNA was counterstained with DAPI. (left) The incidence of γ-H2AX–positive micronuclei (WT, n = 1,463; K243R/+, n = 1,132). (right) Cellular DNA damage in WT and K243R/+ MEFs (WT, n = 1,463; K243R/+, n = 1,132). The results in A–C are from two independent experiments (mean ± SEM). (D) Paraffin-embedded sections of livers from WT or K243R/+ mice after partial hepatectomy were stained with H&E. Three animals each were subjected to partial hepatectomy. Micronuclei in regenerating hepatocytes (arrows) are compared as fold increase on the right: WT, 0.4% (3 out of 693 cells); K243R/+, 2.0% (21 out of 1,069). (E) Micronuclei or nuclear blebs (top, arrows) and lagging chromosomes (bottom) observed in the paraffin-embedded sections of hepatocellular carcinoma from the K243R/+ mice. Bars, 10 µm.