1-day styrene inhalation dose response in C57BL/6 mice (lung)

This data set is #2 of three generated as part of a coordinated series of experiments to examine potential modes of action of Styrene inhalation on lung and liver in male C57Bl/6 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, using a total of three genomic data sets. Dataset #1 exposed C57BL/6 wild-type (WT), CYP2F2 knockout (-/-; KO) and CYP2F21 humanized (2F2-KO + 2F1,2A13,2B6-transgenic, TG) male mice to 0, 40 or 120 ppm styrene at 6 hr/day 5 days/wk for 1 or 4 wk. Lungs were analyzed by whole genome microarrays for each strain at each dose. The second part of the study examined a broader dose response and short term exposure. Male wild type C57Bl/6 mice were exposed to 6 inhalation concentrations of styrene: 0, 1, 5, 10, 20, 40, and 120 ppm for a single 6 hour exposure. This was intended to gain dose-response data at low-observed-adverse-effect-levels (LOAELs) of styrene (≥ 20 ppm) and at no-observed-adverse-effect-levels (NOAELs) of styrene (< 20 ppm). Dataset #2 examined lung gene expression, while dataset #3 examined liver gene expression data from the same animals. Lung gene expression was evaluated in male C57Bl/6 (WT) mice following a single 6-hr inhalation exposure of styrene at 0, 1, 5, 10, 20, 40, and 120ppm