Figure 1.

Regulation of Dox-induced cardiotoxicity by ATM. Atm^−/− and wild-type mice were subjected to a single i.p. injection of saline or Dox (15 mg/kg of body weight) for 7 days to induce cardiotoxicity. (A) HW/BW ratio (n = 7 per group). (B and C) Dox-induced cardiac apoptosis as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining. Immunoreactivity was visualised with diaminobenzidine (brown). Haematoxylin was used as nuclear stain (blue). Arrows indicate representative TUNEL-positive cardiac cells (B). Scale bar, 50 µm. Apoptosis index (percentage of TUNEL-positive nuclei) was calculated as TUNEL-positive nuclei/total nuclei × 100 (%). Apoptosis index of cardiac cells was plotted (n = 3 per group, total of 18 visual fields) (C). (D and E) Echocardiographic analysis (n = 5 per group). M-mode echocardiographic tracings (D) and left ventricular fractional shortening (LVFS) (E) of mice treated with saline or Dox. The results are expressed as means ± SD; *P < 0.05; **P < 0.01; NS: not significant, by two-way ANOVA followed by a post hoc Tukey's multiple comparisons test.