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. 2017 Feb 1;7:41892. doi: 10.1038/srep41892

Figure 5. Impact of ATM and ATR kinase inhibition on DNA synthesis in intestinal crypts after TBI.

Figure 5

Mice received vehicle, 100 mg/kg AZ31, or 75 mg/kg AZD6738 2 h prior to 9 Gy TBI. Small intestine tissues were harvested at the specified timepoints after TBI. For un-irradiated mice, tissues were harvested at 6 h after inhibitor dosing, equivalent to 4 h after TBI. (A) Representative images of bromodeoxyuridine (BrdU) positive IHC staining in the small intestine crypts of vehicle and AZ31 treated, wild-type mice at 4 h after 9 Gy TBI, compared to 0 Gy controls. (B) Enumeration of the number of BrdU positive cells per small intestine crypt in vehicle, AZ31, or AZD6738 treated, wild-type mice at 4 h, 24 h, and 48 h after 9 Gy TBI, compared to 0 Gy controls. (C) Enumeration of the number of BrdU positive cells per small intestine crypt in vehicle, AZ31, or AZD6738 treated, Cdkn1a(p21CIP/WAF1)−/− mice at 4 h after 9 Gy TBI, compared to 0 Gy controls. For BrdU quantitation in both wild-type and Cdkn1a(p21CIP/WAF1)−/− mice, box and whisker plots depict counts from a total of 200 crypts (n = 200), with 100 crypts from each of 2 mice. *p < 0.05, **p < 0.01, ****p < 0.0001. (D) Representative images of p21 positive IHC staining in the small intestine crypts of vehicle, AZ31, or AZD6738 treated, wild-type mice at 4 h after 9 Gy TBI, compared to 0 Gy controls. (E) p21 mRNA expression in the small intestine mucosa of vehicle, AZ31, or AZD6738 treated, wild-type mice at 4 h after 9 Gy TBI, compared to 0 Gy controls. Plots depict 3 technical replicates from one mouse per condition.