Increased IR dosage leads to increased and prolonged induction of molecular senescence markers in p53+/m mice. (A) Six-week-old male p53+/+ and p53+/m mice were irradiated with a dosage curve ranging from 0 to 5 Gy IR and spleens were harvested one week post-irradiation. Western blots show little or no increase in p21 or p16INK4a senescence markers in p53+/+ spleens, but dramatic increases in both markers in the p53+/m spleens. (B) Three-month-old p53+/+, p53+/−, p53−/−, and p53+/m male mice were irradiated with 5 Gy IR and spleens were harvested 6 h post-irradiation. Western blot analysis indicates significant increase in the levels of p16INK4a in p53+/m spleens. Levels of p53 protein induced 6 h post IR are also shown. When normalized to loading control, levels of p53 induced in p53+/m spleens are at least three fold higher than in p53+/+ spleens. Representative blots are illustrated.