Exposure to carbon black nanoparticles during pregnancy aggravates lipopolysaccharide-induced lung injury in offspring: an intergenerational effect.

Carbon black nanoparticles (CBNPs) are one of the most frequently used nanoparticles. Exposure to CBNPs during pregnancy (PrE to CBNPs) can directly induce inflammation, lung injury, and genotoxicity in dams and results in abnormalities in offspring. However, whether exposure to CBNPs during pregnancy enhances the susceptibility of offspring to environmental stimuli remains unknown. To address this issue, in this study, we intranasally treated pregnant mice with mock or CBNPs from gestational day (GD) 9 to GD18, and F1 and F2 offspring were normally obtained. By intratracheal instillation of mice with lipopolysaccharide (LPS) to trigger a classic animal model for acute lung injury, we intriguingly found that after LPS treatment, F1 and F2 offspring after exposure during pregnancy to CBNPs both exhibited more pronounced lung injury symptoms, including more degenerative histopathological changes, vascular leakage, elevated MPO activity, and activation of inflammation-related signaling transduction, compared with F1 and F2 offspring in the mock group, suggesting PrE to CBNPs would aggravate LPS-induced lung injury in offspring, and this effect was intergenerational. We also observed that PrE to CBNPs upregulated the mRNA expression of DNA methyltransferases (Dnmt) 1/3a/3b and DNA hypermethylation in both F1 and F2 offspring, which might partially account for the intergenerational effect. Together, our study demonstrates for the first time that PrE to CBNPs can enhance sensitivity to LPS in both F1 and F2 offspring, and this intergenerational effect may be related to DNA hypermethylation caused by CBNPs.

Arsenite induces ferroptosis in the neuronal cells via activation of ferritinophagy.

Ferroptosis is a novel form of cell death that involves in the pathophysiological process of diverse brain diseases. However, how arsenite induces ferroptosis in the neuronal cells remains unsolved. In this study, by using in vitro and in vivo models, we demonstrated that arsenite was able to trigger ferroptosis in the neuronal cells. Exposure of arsenite for 6 months at 0.5, 5 and 50 mg/L arsenite via drinking water significantly reduced the number of neurons and caused the pathological changes in the mitochondria of hippocampus. Treatment of arsenite elevated the contents of lipid peroxidation products, disrupted the iron homeostasis, altered the expressions of ferroptosis-related proteins in the hippocampus and PC-12 cells. The results also showed that arsenite significantly decreased the expressions of ferritin and NCOA4, but sharply enhanced the level of autophagy marker LC3B, suggesting the activation of ferritinophagy by arsenite. Co-treatment of arsenite with ferroptosis inhibitor ferrostatin-1, or autophagy inhibitors 3-MA and BafA1, all remarkably attenuated the cytotoxic effects of arsenite. These findings not only present a novel mechanism that arsenite triggers ferroptosis in the neuronal cells via activation of ferritinophagy, but also indicate that regulating ferritinophagy to control iron level may provide a clue for prevention against arsenite neurotoxicity.

Lysosomal dysfunction is associated with persistent lung injury in dams caused by pregnancy exposure to carbon black nanoparticles.

AIMS: Carbon black nanoparticles (CBNPs) are widely used in industrial field. Sensitive stages such as pregnancy are assumed to be more susceptible to stimulus, however whether pregnancy exposure to CBNPs (PrE-to-CBNPs) would cause long-term toxic effects in dams and the underlying mechanisms remain poorly addressed. The present study is aimed to determine the long-term toxic effects of PrE-to-CBNPs in dams. MATERIALS AND METHODS: The pregnant mice were randomly divided into control group, low (21 µg/animal), medium (103 µg/animal) and high (515 µg/animal) CBNPs-treated groups. From gestational day (GD) 9 to GD18, the pregnant mice were intranasal exposed. At 49 days after parturition, lung tissues and bronchoalveolar lavage fluid (BALF) were obtained. Weight change, lung histopathology, lung ultrastructural pathology, cell count in BALF, oxidative stress/inflammatory maker and autophagy/lysosome-related protein expression were determined. KEY FINDINGS: PrE-to-CBNPs caused a dose-dependent persistent lung injury in mice even 49 days after parturition, including the deteriorative lung histopathological changes, elevation of oxidative stress marker Nrf-2, HO-1 and CHOP, infiltration of macrophage and increased mRNA expression of inflammatory cytokines in the lung tissues and elevation of cells in BALF. However, PrE-to-CBNPs did not induce significant neutrophil infiltration and fibrosis. Moreover, we found that CBNPs could deposit in the lysosomes and decrease cathepsin D (an important hydrolase in lysosome), which might be associated with the dysfunction of lysosome and autophagy. SIGNIFICANCE: Our study demonstrated that PrE-to-CBNPs could result in long-term lung injury in dams, and lysosomal dysfunction was probably linked to this process.

Synaptic dopamine release is positively regulated by SNAP-25 that involves in benzo[a]pyrene-induced neurotoxicity.

Benzo[a]pyrene (B[a]P) is a ubiquitous neurotoxic pollutant that widely distributes in the natural environment. However, the exact mechanism of B[a]P-induced neurotoxicity has not been well established. As one key synaptic protein, SNAP-25 plays an important role in the regulation of neurotransmitter release, including synaptic dopamine release. In this study, we demonstrated that, after intragastric administration of B[a]P in rats aged postnatal day 5 for 7 weeks, B[a]P significantly increased the level of dopamine and the expression of SNAP-25, dopamine receptor 1 (DRD1) and DRD 3. Moreover, treatment of B[a]P also caused the ultra-structural pathological changes in the cerebral cortex of rats. To further reveal the potential role of SNAP-25 in the regulation of DRDs, we treated the dopaminergic PC-12 cells with 20 µM B[a]P for 24 h. A significant cytotoxicity and apoptosis were observed, and more importantly, we found that SNAP-25, DRD 1 and DRD 3 co-localized in the cells, and down-regulation of SNAP-25 by CRISPR-Cas9 plasmid remarkably reduced the expression of DRD1 and DRD3. Together, our findings suggest that, synaptic dopamine release may be positively regulated by SNAP-25 via its receptors, and thus affecting the neurotoxicity induced by B[a]P.

Exposure to carbon black nanoparticles during pregnancy persistently damages the cerebrovascular function in female mice.

Maternal exposure to carbon black nanoparticles (CBNPs) during pregnancy have been well documented to induce harmful outcomes of offspring on brain function. However, it remains largely unknown whether females exposed to CBNPs during sensitive period of pregnancy can cause the neurotoxic effects on their own body after parturition. In this study, our results showed that pregnancy CBNPs exposure induced the persistent pathological changes in the cerebral cortex tissues and impaired cerebrovascular function of mice manifested by significant alterations of endothelin-1, endothelial nitric oxide synthase, vascular endothelial growth factor-A and ATP-binding cassette transporter G1. Intriguingly, we observed that these deleterious effects on brain and cerebrovascular functions in mice could persist for 49 days after delivery of pups. By using in vitro human umbilical vein endothelial cells, we further verified the potential vascular dysfunction after CBNPs exposure. In summary, our results provide the first evidence that pregnancy CBNPs exposure-induced brain pathological changes and cerebrovascular dysfunction can persist for a relative long time. These finding suggest exposure to CBNPs during sensitive stages of pregnancy may not only show the harmful effects on offspring neurodevelopment, but also result in the irreversible brain damage on mother body.

Gas chromatography-mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure.

Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3-week-old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography-mass spectrometry (GC-MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As-induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.

m6A Demethylase FTO Regulates Dopaminergic Neurotransmission Deficits Caused by Arsenite.

Arsenite exposure is known to increase the risk of neurological disorders via alteration of dopamine content, but the detailed molecular mechanisms remain largely unknown. In this study, using both dopaminergic neurons of the PC-12 cell line and C57BL/6J mice as in vitro and in vivo models, our results demonstrated that 6 months of arsenite exposure via drinking water caused significant learning and memory impairment, anxiety-like behavior and alterations in conditioned avoidance and escape responses in male adult mice. We also were the first to reveal that the reduction in dopamine content induced by arsenite mainly resulted from deficits in dopaminergic neurotransmission in the synaptic cleft. The reversible N6- methyladenosine (m6A) modification is a novel epigenetic marker with broad roles in fundamental biological processes. We further evaluated the effect of arsenite on the m6A modification and tested if regulation of the m6A modification by demethylase fat mass and obesity-associated (FTO) could affect dopaminergic neurotransmission. Our data demonstrated for the first time that arsenite remarkably increased m6A modification, and FTO possessed the ability to alleviate the deficits in dopaminergic neurotransmission in response to arsenite exposure. Our findings not only provide valuable insight into the molecular neurotoxic pathogenesis of arsenite exposure, but are also the first evidence that regulation of FTO may be considered as a novel strategy for the prevention of arsenite-associated neurological disorders.

Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats.

Benzo(a)pyrene (BaP) is a widespread environmental contaminant that has been associated with neurotoxicity in mammals. It has strong toxic effects on the developing central nervous system. Cerebellum is associated with locomotor activity and anxiety behavior, but there is very little research about the toxic effects of BaP in cerebellum. The present study aims to investigate the global influence of BaP subacute exposure on the metabolome of rat cerebellum. Male neonatal rats (postnatal day 5) were divided into two groups: control group and BaP-treated group (2 mg/kg/day for 7 weeks). Open field test and transmission electron microscopy were performed to analyze neurobehavior and ultramicrostructure alteration. Gas chromatography-mass spectrometry (GC-MS) was used to analyze metabolites of the cerebellum in both groups. The results revealed that postnatal exposure to BaP promoted pathological changes in the cerebellum and increased locomotor and anxiety activities in early adulthood. Twenty differential significant metabolites were identified by multivariate statistical analysis. Further metabolic pathway impact analysis and network analysis suggested that the primary metabolic pathways affected included pathway involved in energy metabolism, methionine and cysteine metabolism, and glutathione metabolism. These findings suggest that BaP-induced cerebellum injury may be correlated with metabolic changes and provide an area to target to reduce the negative effects of BaP.

Disruption of glutamate neurotransmitter transmission is modulated by SNAP-25 in benzo[a]pyrene-induced neurotoxic effects.

Benzo[a]pyrene (B[a]P), a ubiquitous chemical contaminant in the environment, is a well-established neurotoxicant to human. However, the molecular mechanisms for B[a]P neurotoxicity are still unclear. In the present study, after treating Sprague-Dawley rats with 0.02, 0.2 and 2.0mg/kg/day B[a]P for 7 weeks [from postnatal day (PND) 5 to PND54], our results showed that B[a]P exposure caused a significant deficits in learning and memory function. By using U87 cells as in vitro model, the significant cytotoxicity and the induction of apoptosis caused by B[a]P were further verified. More importantly, we demonstrated for the first time that B[a]P exposure caused the disruption of glutamate (Glu) neurotransmitter transmission by decreasing the level of Glu, reducing the expression of Glu receptors (GluR1 and GluR2), enhancing the level of SNAP-25, widening the synaptic cleft, and ultimately producing the neurotoxic effects in both cells and animals. Our results will provide novel evidence to reveal the possible role of SNAP-25 in B[a]P-induced neurotoxicity and may be helpful for searching the potential strategy for the prevention measures against B[a]P neurotoxicity.

Effects of benzo(a)pyrene exposure on the ATPase activity and calcium concentration in the hippocampus of neonatal rats.

OBJECTIVES: To investigate whether postnatal benzo(a)pyrene (B(a)P) exposure caused the impairments on the process of neurodevelopment and the alteration in the calcium medium in the neonatal rats. MATERIAL AND METHODS: Eighty neonatal Sprague Dawley (SD) rats were randomly divided into 5 groups (untreated control group, vehicle group, 0.02 mg/kg, 0.2 mg/kg and 2 mg/kg B(a)P-exposed group). Rats were treated with B(a)P by the intragastric administration from postnatal day (PND) 4 to 25. Morris water maze (MWM) was employed to observe the spatial memory of rats. The activity of calcium adenosine triphosphatase (Ca2+-ATPase), sodium-potassium adenosine triphosphatase (Na+-K+-ATPase) and calcium-magnesium adenosine triphosphatase (Ca2+-Mg2+-ATPase) in the hippocampus were detected by commercial kits. Fura-2 pentakis(acetoxymethyl) (Fura-2/AM) probe and reactive oxygen species (ROS) reagent kit were used for measuring the concentration of Ca2+ and ROS in the hippocampus synapse, respectively. RESULTS: Rats exposed to B(a)P resulted in the deficits in the spatial memory manifested by the increased escape latency and decreased number of crossing platform and time spent in target quadrant in comparison with the control groups. Benzo(a)pyrene exposure caused the significant decrease in the ATPase activity in the hippocampus and caused Ca2+ overload in the synaptic, besides, the ROS concentration increased significantly which may further induce neurobehavioral impairment of the neonatal rats. CONCLUSIONS: Our findings suggest that postnatal B(a)P exposure may cause the neurobehavioral impairments in the neonatal rats, which were mediated by the decreased ATPase activity and elevated Ca2+ concentration. Int J Occup Med Environ Health 2017;30(2):203-211.

Effects of coke oven emissions and benzo[a]pyrene on blood pressure and electrocardiogram in coke oven workers.

OBJECTIVE: To evaluate the effects of occupational exposures to coke oven emissions (COEs) and benzo[a]pyrene (B[a]P) on the prevalence of hypertension and abnormal electrocardiogram (ECG) in coke oven workers. METHODS: We included 880 coke oven workers and 710 oxygen employees in the exposed and control groups, respectively. Blood pressure (BP), ECG, blood lipid levels, and glucose levels of all subjects were measured. COE and B[a]P concentrations at the bottom, side, and top of the oven and control plants were estimated by weighing and high-performance liquid chromatography. RESULTS: The COE concentration at the top and side was higher than that at the bottom (P < 0.05). The levels of B[a]P at the top and side significantly exceeded the limit value. Abnormal BP, ECG, the detection ratio of hypertension and left ventricular high voltage were significantly greater in the exposed group than in the control group (P < 0.05). The logistic regression analysis results revealed that age and B[a]P exposure were risk factors for hypertension in coke oven workers (P < 0.05) and both were risk factors for abnormal ECG (P < 0.05). Moreover, B[a]P exposure, age, and gender were risk factors for impaired fasting glucose in coke oven workers (P < 0.05). CONCLUSIONS: B[a]P and COE exposures are risk factors for hypertension and abnormal ECG in coke oven workers.

[Effect of Benzo [α]pryene and Butylated Hydroxylanisole on Learning and Memory in Rats].

OBJECTIVE: To investigate the neurotoxic effect of benzo[α]pryene (B[α]P) and protective effect of butylated hydroxyl anisole (BHA) on learning and memory in hippocampus of rats. METHODS: Ninety male, SD rats were randomly divided into blank control group, solvent control group, B[α]P exposed group [(2 mg/(kg x d)], BRA group [50 mg/(kg x d)] and B[α]P + BHA combined group. Rats were given the appropriate dose oral treatment according to body mass and group (the same volume of saline and peanut oil were given to blank and solvent control group, respectively) for 90 d. After 90 d exposer, Morris water maze (MWM) was conducted to estimate rats' learning and memory ability. The level of malonaldehyde (MDA), superoxide dismutase (SOD) activity, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity and Ca2+ concentration were measured after rats were sacrificed and brain tissue were removed. RESULTS: Behavioral test results showed that the escape latency of B[α]P exposed group were significantly increased than other groups (P < 0.05); however, the number of crossing platform (4.13 ± 0.78) were decreased significant. The level of MDA [( 2.46 ± 0.39) nmol/mg prot.] and Ca2+ concentration [(146.3 ± 16.68) nmol/L] in the B[α]P exposed group increased significant, while the activity of Na(+)-K(+)-ATPase and SOD [(76.1 ± 11.42) nmol/mg prot.] were significantly decreased. Compared with B[α]P group, each index in B[α]P+ BHA combined group improved significantly (P < 0.05), besides, there were no statistically difference when compared with solvent control group. CONCLUSION: The neurotoxic effect of B[α]P may be related to the decrease of ATPase activity and the increase of Ca2+ concentration in hippocampus, while BHA can prevent these damages.

[Effects of benzo(a)pyrene exposure on the ATPase activity and content of Ca²âº in the hippocampus of neonatal SD rats].

OBJECTIVE: To investigate the effect of benzo(α)pyrene on the ATPase activity and content of Ca²âº in the hippocampus of neonatal SD rats. METHODS: Sixty male and 60 female 4-days-old neonatal SD rats were randomly divided into 5 groups (n=24): a blank control group, a vehicle control group (peanut oil), 3 benzo(α)pyrene groups (0.02, 0.2 and 2 mg/kg, respectively). SD rats were given benzo(α)pyrene (dissolved in peanut oil) by gavage daily from postnatal day 4 (PND4) to PND20. The nerve reflex, the condition of neuro-muscle development and motion function were examined in the period of treatment. The colorimetric technique was used to detect the activity of Ca²âº-ATPase and Ca²âº-Mg²âº-ATPase in hippocampus after the treatment. The concentration of Ca²âº of synapse in the hippocampus of rats was detected by fluorescent labeling. RESULTS: The results from the behavior tests showed that duration of surface reflex latency in rats with medium dose of benzo(α)pyrene was longer compared with that in the control group in PND12. The duration of surface reflex latency in rats with high dose of benzo(α) pyrene is longer in PND 14 and PND 16 compared with that in the control group (P<0.05). Compared with the rats in the control group, the activities of Ca²âº-Mg²âº-ATPase and Ca²âº-ATPase in hippocampus in rats with high dose benzo(α) pyrene were significantly decreased, and the degree in the decrease of Ca²âº-ATPase activity was dose-dependent (P<0.05). The contents of Ca²âº in the hippocampus in rats with medium or high dose of benzo(α) pyrene were significantly increased compared with that in the control group (P<0.05), which showed a dose-dependent manner (P<0.05). CONCLUSION: Benzo(α)pyrene exposure led to the decrease in ATPase activity as well as Ca²âº overload of the synapse in the hippocampal tissue, which in turn results in the nerve damage of newborn SD rats.

Adverse effect of sub-chronic exposure to benzo(a)pyrene and protective effect of butylated hydroxyanisole on learning and memory ability in male Sprague-Dawley rat.

Previous studies demonstrate that benzo(a)pyrene (B(a)P) can affect hippocampal function and cause spatial cognition impairment. However, the mechanism is incomplete. Some evidence implies that B(a)P may cause an oxidative damage linking to the function of the hippocampus and antioxidant can prevent the oxidative damage in rats, but the ATPase and Ca(2+) in the hippocampus and the protective effect of butylated hydroxyanisole (BHA) have not been studied. This study aimed to investigate the damage of toxicity further induced by B(a)P in hippocampus and the protective effect of BHA. Ninety-six male Sprague-Dawley (SD) rats were randomly divided into four groups (solvent control group, BHA-group, B(a)P-exposed group and B(a)P-BHA-combination group), with daily administration for 90 days. Morris water maze (MWM) was employed to evaluate the learning and memory ability. The levels of malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)ATPase activity in hippocampus were measured by commercial kits. The concentration of Ca(2+) in rat hippocampus was detected by fluorescent labeling. In behavior test it showed that there was an adverse effect on rats in the B(a)P -group. The levels of MDA content and Ca(2+) content were significantly increased in the B(a)P group, while the activities of SOD and ATPase were significantly decreased. In the B(a)P-BHA group, the change of each index diminished significantly. The results suggested that the neurobehavioral toxicity of B(a)P might have a close relationship with oxidative damage, resulted in decreasing of ATPase activities and increasing of Ca(2+) concentration in the hippocampus. Furthermore, BHA can prevent these damages.

[Effects of benzo(a)pyrene exposure on oxidative stress and ATPase in the hippocampus of rats].

OBJECTIVE: To investigate the effects of benzo[a]pyrene (B[a]P) exposure on the behaviors and hippocampal oxidative stress and ATPase in rats and the molecular mechanism of neurobehavioral toxicity of B[a]P. METHODS: A total of 120 male SD rats (21 days old) were randomly and equally assigned to five groups: blank control group, vegetable oil (solvent control) group, and 2.5, 5, and 10 mg/kg B[a]P exposure groups. The rats in B[a]P exposure groups were injected intraperitoneally with B[a]P once a day for 4 consecutive weeks. Then, Morris water maze and shuttle box were used to evaluate the learning and memory abilities of rats; colorimetric assay was used to measure the activities of superoxide dismutase (SOD), Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase and the content of malonaldehyde (MDA) in the hippocampus; the concentration of Ca(2+) in the hippocampus was measured by fluorescent labeling. RESULTS: Compared with the blank control group and solvent control group, the B[a]P exposure groups exhibited significant increases in escape latency, active avoidance response latency, and passive avoidance response latency and significant decreases in number of platform crossings and active avoidance response frequency in the last test (P < 0.05 for all comparisons), with a dose-effect relationship. In addition, the B[a]P exposure groups had significantly lower activities of SOD, Na(+)/K(+)-AT-Pase, and Ca(2+)/Mg(2+)-ATPase and significantly higher MDA level and Ca(2+) concentration than the blank control group and solvent control group (P < 0.05 for all comparisons), with a dose-effect relationship. CONCLUSION: The neurobehavioral toxicity of B[a]P may be related to increased oxidative stress and decreased activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in the hippocampus of rats.

Neurotoxic effect of subacute benzo(a)pyrene exposure on gene and protein expression in Sprague-Dawley rats.

Benzo(a)pyrene (B[a]P) is an environmental carcinogen that induces tumors in many animal species, but the neurotoxic effects of B[a]P have not been well studied. In the present study, we investigated the effects of subacute exposure to B[a]P in Sprague-Dawley (SD) rats. Male rats received daily injections of either B[a]P (0, 1, 2.5, or 6.25mg/kg, i.p.) or vehicle for 45 days. Exposure to B[a]P affected the behavior of rats in the Morris water maze test. Gene microarray and real-time PCR analyses revealed that exposure to B[a]P affected signal transduction in the rat hippocampus. Protein microarray analysis revealed that altered protein expression played a role in cell death in the functional annotation cluster analysis. Finally, major vault protein was found to display low cDNA and protein expression levels. The present study explored some of the possible mechanisms underlying B[a]P neurotoxicity and provided evidence that B[a]P plays a neurotoxic role in rats.

The effect of occupational exposure to benzo[a]pyrene on neurobehavioral function in coke oven workers.

BACKGROUND: Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (B[a]P), known as an indicator species for PAH contamination, is a neurobehavioral toxicant. The purpose of the study was to evaluate the relationship between B[a]P exposure, a B[a]P-related urinary metabolite and neurobehavioral function among coke oven workers. METHODS: Coke oven workers and oxygen factory workers participated in this study. B[a]P exposure was monitored by air sampling pump, and urinary 1-hydroxypyrene (1-OHP) level was detected with high performance liquid chromatography (HPLC). A questionnaire and the neurobehavioral core test battery (NCTB) were administered to all subjects. RESULTS: B[a]P-exposed workers were found to have higher urinary 1-OHP levels and worse NCTB performances on eight items than control workers. B[a]P concentrations were higher in the coke oven plant than that in the controls' workplace. The performances on simple reaction time, correct pursuit aiming, and error pursuit aiming decreased with increasing airborne B[a]P in coke oven workers. There were significant correlations between urinary 1-OHP level and six items of the NCTB. CONCLUSIONS: Occupational exposure to B[a]P is associated with neurobehavioral function impairment in coke oven workers.

Effects of subchronic exposure to benzo[a]pyrene (B[a]P) on learning and memory, and neurotransmitters in male Sprague-Dawley rat.

The harmful effects of the environmental carcinogen, benzo[a]pyrene (B[a]P), on mammalian neurodevelopment and behavior as yet remain unclear. Several studies have suggested that B[a]P impairs learning and memory. In the present investigation, we investigated the effects of subchronic exposure to B[a]P on rats. Male rats received daily injection of B[a]P (0, 1.0, 2.5, and 6.25 mg/kg, i.p.) or vehicle for 13 weeks. Employing the Morris water maze (MWM) test, we observed that rats exposed to either 2.5 mg/kg or 6.25 mg/kg B[a]P had modified behavior compared to controls as indicated by the increased mean latencies, the decreased number of crossing platform and the decreased swimming time in the target area. B[a]P treatment decreased the levels of malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), acetylcholine (ACh), choline acetyltransferase (ChAT), and increased the activity of acetylcholinesterase (AChE). Endogenous monoamine levels, norepinephrine (NE), adrenaline (A), dopamine (DA) and 5-hydroxytryptamine (5-HT) and their selected metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured using high performance liquid chromatography (HPLC). B[a]P at both doses, 2.5 and 6.25 mg/kg, increased NE, DA, DOPAC and 5-HT content in the hippocampus. Our results suggested a close link between the modified levels of neurotransmitters in the hippocampus and the impaired behavioral performance, indicating that B[a]P is a potential neurotoxic pollutant.