Dose makes poison: Insights into the neurotoxicity of perinatal and juvenile exposure to environmental doses of 16 priority-controlled PAHs.

Whether chronic exposure to environmental doses of polycyclic aromatic hydrocarbons (PAHs) can lead to neurotoxic effects is still unclear. Hence, the neurotoxic effects of perinatal and juvenile exposure to 16 priority-controlled PAHs were investigated. The mice were treated with 0, 0.5, 18.75, 50, 1875 µg/kg/day of PAHs corresponding to various population exposure concentrations from gestation to postnatal day 60. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hippocampal and cortical neurotransmitter levels were determined using liquid chromatography-tandem mass spectrometry. Typical indicators or outcome of neurotoxicity, including, spatial learning and memory ability, hippocampal long-term potentiation (LTP) and dendritic spine density were evaluated via Morris water maze tests, electrophysiological experiments and Golgi-Cox assays, respectively. The results showed that exposure to different levels of PAH could not increase oxidative DNA damage level. Mice exposed to 0.5, 50 and 1875 µg/kg/day PAHs had significantly longer escape latency than the control group only on the 1st day (p < 0.05). The number of platform crossings and the time spent in target quadrant were similar between the control and the PAHs-exposed mice. Compared with the control mice, only those exposed to 50 µg/kg/day PAHs had significantly lower LTP in hippocampal CA1 region and dendritic spine density in hippocampal DG region (p < 0.05). Except for serotonin, no significant difference in hippocampal and cortical neurotransmitter concentrations was observed between the control and PAHs-exposed groups. Taken together, perinatal and juvenile exposure to environmental doses of PAHs had no profound effect on spatial learning and memory abilities, hippocampal LTP, dendritic spines density, and neurotransmitter levels. These unexpected findings were quite different from previous in vivo studies which commonly used 2-3 orders of magnitude higher PAHs doses to treat animals. Thus, the environmental dose is a crucial reference for future toxicological research to reveal the actual toxic mechanisms and human health effects of PAHs exposure.

Association among blood BPDE-DNA adduct, serum interleukin-8 (IL-8) and DNA strand breaks for children with pulmonary diseases.

Exposure to benzo[a]pyrene (B[a]P) may be a risk factor for pulmonary diseases. To investigate the correlations among B[a]P exposure level, DNA strand breaks and pulmonary inflammation, we recruited 83 children diagnosed with pulmonary diseases and 63 healthy children from Guangzhou, China. Results showed that the levels of Benzo[a]pyrene diol epoxide (BPDE) DNA adduct in blood and IL-8 in serum in case group were significantly higher than those in control group (p < 0.01). Moreover, levels of atmospheric B[a]P in case group was about twice of those in control group, which was consistent with the levels of BPDE-DNA adduct in blood. Significant positive correlations were observed among the levels of BPDE-DNA adduct, IL-8 and DNA strand breaks (p < 0.05). Our findings indicate that environmental air is an important exposure source of B[a]P and higher B[a]P exposure may contribute to the occurrence of pulmonary inflammation and lead to high health risks.

Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene may impair lung function by increasing oxidative damage and airway inflammation in asthmatic children.

As previous studies found that the direct associations between urinary polycyclic aromatic hydrocarbon (PAH), benzene and toluene (BT) metabolites and the decreased lung function were not conclusive, we further investigated relationship of oxidative damage and airway inflammation induced by PAHs and BTs exposure with lung function. A total of 262 children diagnosed with asthma and 72 heathy children were recruited. Results showed that asthmatic children had higher levels of PAHs and BTs exposure, as well as Malonaldehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) compared with healthy children. Furthermore, binary logistic regression showed that each unit increases in level of urinary 2-&3-hydroxyfluorene (2-&3-OHF), 2-hydroxyphenanthrene (2-OHPhe), 1-hydroxyphenanthrene (1-OHP) and S-phenylmercapturic acid (S-PMA) were significantly associated with an elevated risk of asthma in children with odds ratios of 1.5, 2.3, 1.7 and 1.4, respectively, suggesting that PAHs and BTs exposure could increase the risk of asthma for children. Neither PAH nor BT metabolite could comprehensively indicate the decreased lung function as only 2-&3-OHF and 1-OHP were significantly and negatively correlated with forced vital capacity (FVC). Moreover, levels of most individual PAH and BT metabolite were significantly correlated to MDA and 8-OHdG. Further hierarchical regression analysis indicated that MDA and 8-OHdG levels did not show significant effects on the decreased lung function, suggesting that they are not the suitable biomarkers to indirectly indicate the altered lung function induced by PAHs and BTs. Urinary 2-OHPhe and 1-&9-hydroxyphenanthrene (1-&9-OHPhe) were significantly correlated with fractional exhaled nitric oxide (FeNO). Moreover, FeNO significantly contributed to decreased lung function and explained 7.7% of variance in ratio of forced expiratory volume in 1 s (FEV1) and FVC (FEV1/FVC%). Hence, FeNO, rather than oxidative damage indicators or any urinary PAH and BT metabolite, is more sensitive to indirectly reflect the decreased lung function induced by PAHs and BTs exposure for asthmatic children.