Lung gene expression after long-term styrene inhalation in three strains of C57BL/6 mice, and CD-1 mice

Lung gene expression after long-term (26 weeks, 52 weeks, 78 weeks & 104 weeks) styrene inhalation exposure at a single concentration (120ppm) in three strains of C57BL/6 mice -- wild-type (WT), CYP2F2 knockout (KO), and CYP2F1 humanized (TG) mice, and CD-1 mice. These data examine transcriptomic changes in lung tissue after long-term styrene inhalation in male C57Bl/6 and CD-1 mice. Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice after long-term exposure to styrene. Mice strains exposed were C57BL/6 wild-type (WT), CYP2F2 knockout (-/-; KO) and CYP2F21 humanized transgenic (2F2-KO + 2F1,2A13,2B6-transgenic, TG), and CD-1 male mice using 120 ppm styrene at 6 hr/day 5 days/wk for 26, 52, 78 and 104 weeks. Lungs were analyzed by Affymetrix whole genome microarrays for each strain relative to sample time-specific vehicle controls for each strain. A total of 154 male C57BL/6 and CD-1 mice were exposed to a single inhalation dose of styrene (120ppm) for 26, 52, 78 & 104 weeks. For each treatment, a total of from 2 to 10 biological replicates (both treated animals and corresponding strain- & time-specific vehicle controls) were used, from 3 strains of C57Bl/6 mice: wild type (WT), CYP2F2(-/-) knock-out (KO) and CYP2F2(-/-),2F1,SA13,2B6 transgenic (TG), and CD-1 mice. A _Tu in a CEL file name indicates the presence of tumors or tumorous lesions observed in the animal, but tumor-specific lung tissue was not separately assayed.