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. Author manuscript; available in PMC: 2016 Mar 15.
Published in final edited form as: Clin Cancer Res. 2014 Dec 23;21(6):1466–1476. doi: 10.1158/1078-0432.CCR-14-2072

Figure 6. DNA damage in AKR1B8 −/− mice.

Figure 6

Genome-wide Exome sequencing analyses of WT and AKR1B8 −/− colitis mucosa and tumors (n=2 each) were conducted as described in Materials and Methods. (A) Single homozygous nucleotide mutants. (B) Conventional DNA sequencing of DOX1 and MXD1 tumor suppressor genes, confirming the point mutations. (C) Transitional and transversional point mutations. *, P<0.05 and **, P<0.01 compared to wild type control. Statistical significance was tested by Student’s t test. (D) Hypothetic model of AKR1B8 in colitis and associated dysplastic lesions. AKR1B8 deficiency reduces long chain fatty acid/lipid synthesis from butyrate, which diminishes biomembrane assembly and cell proliferation. The AKR1B8 deficiency also leads to accumulation of toxic carbonyl compounds, which, together with oxidative stress, forms a vicious cycle, leading to DNA damage and subsequent dysplastic lesions. AKR1B8 may also affect proinflammatory cytokine expression via a mechanism unknown yet.