Fig. 1

Experimental designs. Experiment 1–1 was for a dose-finder for Experiment 1–2 and sampling of the colon mucosa, and three concentrations (1.5%, 2.0%, and 2.5%) of DSS were tested for male and female C57BL/6 J mice. Four males and four females from the untreated and DSS groups were used to analyzing the DNA adducts. Based on Experiment 1–1, the concentrations of 2.0% and 2.5% DSS were initially selected for male and female C57BL/6 J mice in Experiment 2, respectively. As one female mouse was euthanized due to poor health conditions after treatment with DSS, the concentration of DSS was reduced from 2.5% to 2.0%. Colon mucosa was collected from two males and two females from the untreated group, and four males and three females from the DSS group to analyze DNA adducts. The treatment regimen of Experiment 2 was determined based on the data from Experiment 1–2, and animal conditions such as clinical signs, stool, and body weight so that mortality might be minimal. Male and female Polk^+/+ and Polk^−/− mice were administered 2.0% DSS for six consecutive days and two consecutive days, separated by a 16-day DSS treatment-free interval period. At week 19 (defining the first week of the experiment as week 0), surviving mice were necropsied to collect colon samples for histopathology and mutation assays, as indicated in the text table