Figure 11.

Principal components analysis (PCA) and Volcano plots for untargeted DNA adductomic analysis from DNA of kidneys and livers from the control (CTRL) and rats treated (TRT) with a 13-carcinogen mixture 24 h following dosing. The PCA plots are the putative DNA aglycone adduct intensities of A) rat kidney and (B) liver. The data were clustered by PCA using the ropls R library. Black, red, and blue ellipses represent 95% CI ellipses for total, dosed, and control samples. The volcano plots of (C) kidney and (D) liver are reported as −1*log(p value) versus log2 fold change of MS² intensities for dosed over control groups for DNA adducts present in at least 50% of the dosed group and a mean intensity over 10,000 counts in either the control or carcinogen-dosed groups. Grey dots represent putative DNA adducts detected in the kidney or liver tissues. Red dots show wSIM-City identified and validated known DNA adducts detected. The blue lines mark DNA adduct intensities (as log 2 FC of −1 or 1) and Student’s t-test (p-value < 0.1 expressed as −1 * log (p-value), one-sided, equal variances). Note, the signal intensities for several known DNA adducts identified at low abundance by targeted MS² in the dosed animals were detected in <50% of the sample by wide-SIM/MS² and filtered out (p-value >0.1). The DNA adduct signals were manually added back to the volcano plot data for visualization purposes.