Radiation-induced accumulation of p53 protein (A-H) and apoptosis (a-h) in mouse mammary glands. Trp53+/+ mice were treated with placebo or E+P either neonatally (10 to 24 days old) or when mature (6 to 8 weeks) and then were irradiated to examine nuclear accumulation of p53 and TUNEL labeling as indicators of p53 activity. Responses were also examined in mammary tissues from nulliparous mice (AMV = age-matched virgin with parous) and following a full-term pregnancy (parous). The absence of staining in Trp53-/- tissues ensures the specificity of p53 immunostaining (A, B) and p53 dependence of TUNEL staining (a, b) in placebo- and E+P-treated mice, respectively. Mammary glands from Trp53+/+ mice treated with placebo, either neonatally or when mature, exhibited low levels of p53 and TUNEL labeling – (C, E) and (c, e), respectively – and were similar to age-matched virgins (G, g). In contrast, both p53+ nuclei and TUNEL labeling were prevalent in the mammary tissues from Trp53+/+ mice treated with E+P either neonatally or at maturity – (D, d) and (F, f), respectively – and were similar to glands from parous mice (H, h). All images were taken at × 400. E+P, estradiol and progesterone; IHC, immunohistochemistry; Trp53, transformation-related protein 53 (gene in mouse encoding the p53 tumor suppressor protein); TUNEL, terminal uridine deoxynucleotidyl transferase dUTP nick-end labeling.