Figure 3
In vitro and in vivo assessment of induction of biologically relevant pathways by EHC-6802. (A) Aryl hydrocarbon receptor activation in vitro. H1L1.1c2 cells were exposed to vehicle, benzo(a)pyrene, EHC-6802 particles, and TiO2, and luciferase activity was determined. Values represent the mean ± SEM of triplicate determinations. (B) Relative basal mRNA levels of CYP1A1 and preproET-1 in the lungs of unexposed WT and TNF mice as measured by real-time PCR. Results are expressed as geometric mean ± SD (n = 4 animals/group). (C) PM effects on CYP1A1 mRNA levels in vivo. SP-C/TNF-α (TNF) mice and their wildtype (WT) littermates were exposed to 0 or 42 mg/m3 EHC-6802 and euthanized 0 or 24 h post-exposure. Real-time PCR was used to determine expression. Results are expressed as geometric mean ± SD (n = 5 animals/group). *Treatment main effect, p = 0.05, one-tailed. (D) PreproET-1 mRNA levels in WT and TNF mice 0 and 24 h after exposure to EHC-6802. *Treatment main effect, p = 0.04, one-tailed.