Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

Abstract

BackgroundLittle is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.ResultsLiver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay.ConclusionsOur results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0238-9) contains supplementary material, which is available to authorized users.

Physicochemical predictors of Multi‐Walled Carbon Nanotube–induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi‐Walled Carbon Nanotubes in mice

“…Instead, genotoxicity was assessed in the main target organs for translocated MWCNT, liver and spleen. We have recently shown that carbon black‐induced genotoxicity in liver is caused by translocation of particles . In the current study, only one MWCNT, NRCWE‐040, induced DNA strand breaks in liver.…”

Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties

“…DNA damage in BAL and lung tissue may be caused by particles, metal ions, or PAHs released from the particles. DNA damage in the liver may be caused by primary genotoxicity caused by translocated particles [22] and by PAHs released into systemic circulation [71,72]. In the current study, particleinduced DNA strand break levels in the liver on day 90 and in lung on day 28 correlated with particle-induced ROS, whereas PAH levels did not correlate with DNA strand break levels.…”

“…Hence, the physicochemical characteristics of the emitted particles, such as content of PAH, metals and ratio of elemental and organic carbon [14,16,17], depend on engine combustion conditions. Particle size and thereby speci c surface area (SSA) is a driver of pulmonary in ammation [18] and acute phase response [19,20] whereas certain metals and PAH, as well as ROS formation are linked to genotoxicity [21,22,23]. Several PAH compounds including benzo[a]pyrene are classi ed as carcinogenic or possibly carcinogenic by IARC [24].…”

Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice

“…For example, TiO 2 (Aeroxide P25®) (same material as used in our present study) induced micronuclei and DNA strand breaks in peripheral blood in adult male mice exposed to 500 mg/kg TiO 2 NPs of 21 nm size through drinking water for 5 d [14], but the effect was not analyzed in liver. With the same material and intravenous injection route, Dobrzynska et al [4] detected increase of micronuclei in bone marrow polychromatic erythrocytes of mice only at 24 h but not later at 7 and 28 d. Modrzynska et al [28] investigated the DNA strand breaks in the liver of mice treated with TiO 2 NPs (NanoAmor, 10.5 nm) by intratracheal instillation, intravenous injection or oral gavage at a single dose of 162 μg/mouse, and did not find DNA damages in liver tissue on day 1, 28 or 180 after the exposure by any administration routes, though there was a significant increase in the level of DNA damages in lung tissue on day 180 following intratracheal instillation. These reports suggested that TiO 2 NPs may induce transient DNA damages in tissue such as blood cells, but not in liver.…”