1-Nitropyrene Induced Reactive Oxygen Species-Mediated Apoptosis in Macrophages through AIF Nuclear Translocation and AMPK/Nrf-2/HO-1 Pathway Activation.

1-Nitropyrene (1-NP), one of the most abundant nitropolycyclic aromatic hydrocarbons (nitro-PAHs), is generated from the incomplete combustion of carbonaceous organic compounds. 1-NP is a specific marker of diesel exhaust and is an environmental pollutant and a probable carcinogen. Macrophages participate in immune defense against the invasive pathogens in heart, lung, and kidney infection diseases. However, no evidence has indicated that 1-NP induces apoptosis in macrophages. In the present study, 1-NP was found to induce concentration-dependent changes in various cellular functions of RAW264.7 macrophages including cell viability reduction; apoptosis generation; mitochondrial dysfunction; apoptosis-inducing factor (AIF) nuclear translocation; intracellular ROS generation; activation of the AMPK/Nrf-2/HO-1 pathway; changes in the expression of BCL-2 family proteins; and depletion of antioxidative enzymes (AOE), such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) These results indicate that 1-NP induced apoptosis in macrophages through AIF nuclear translocation and ROS generation due to mitochondrial dysfunction and to the depletion of AOE from the activation of the AMPK/Nrf-2/HO-1 pathway.

Seasonal characteristic composition of inorganic elements and polycyclic aromatic hydrocarbons in atmospheric fine particulate matter and bronchoalveolar lavage fluid of COPD patients in Northeast China.

OBJECTIVE: To explore the composition characteristics of atmospheric fine particulate matter (PM2.5) and bronchoalveolar lavage fluid (BALF), and their impact on the development of chronic obstructive pulmonary disease (COPD). METHODS: The atmospheric PM2.5 samples and BALF samples from COPD patients were collected from June 2, 2017 to October 30, 2018, and allocated into a high-risk of PM2.5 inhalation group and a low-risk PM2.5 inhalation group according to the heating season in Harbin. Inorganic elements were detected by ICP-MS, and polycyclic aromatic hydrocarbons (PAHs) were detected by GC/MS. RESULTS: Twenty-six inorganic elements were found in 54 BALF specimens. There was a high correspondence in inorganic elements between BALF and atmospheric PM2.5. Trace elements Cr, Mn, V, and Co, and toxic trace elements Al, Pb, Cd, As, and Ag were above the upper limit of normal blood. There were significant higher K, Ti, Fe, Co, Cu, Se, Rb, Ag, and Sb in BALF of the high-risk PM2.5 inhalation group (p < 0.05). Sixteen PAHs were detected in 32 BALF samples. The main components of BALF and atmospheric PM2.5 were the high molecular weight PAHs, and the species and concentration of PAHs in BALF and atmospheric PM2.5 are highly consistent. CONCLUSION: The types and concentrations of inorganic elements and PAHs in BALF of COPD patients are highly consistent with those of atmospheric PM2.5. The sustained high concentrations of Benzo(a)anthracene, Chrysene, Benzo(b)Fluoranthene, Benzo(k)Fluoranthene, Indeno(123-c,d)Pyrene, and Benzo(a)Pyrene in BALF of COPD patients may have long-term adverse effects on COPD patients.

Effects of exposure to polycyclic aromatic hydrocarbons combined with high-risk human papillomavirus infection on cervical intraepithelial neoplasia: A population study in Shanxi Province, China.

High-risk human papillomavirus (HR-HPV) infection is a major etiological agent in the progression of cervical intraepithelial neoplasia (CIN) and cervical cancer. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic pollutants that exist widely in the environment. We hypothesized that PAHs exposure was related to the progression of cervical cancer, and could increase the effect of HR-HPV on CIN. We investigated the effects of PAHs exposure combined with HR-HPV infection on CIN in community population in Shanxi Province, China. A total of 2,285 women were enrolled into the study. HR-HPV genotypes were detected by flow-through hybridization technology. 1-hydroxypyrene (1-OHP) was detected by high-performance liquid chromatography. The top three HR-HPV genotypes were 16, 58 and 52 in turn. With unconditional logistic regression analysis, we found that HR-HPV infection (adjusted odds ratio [aOR] = 4.08, 95% confidence interval [CI]: 3.00-5.54), HPV16 infection (aOR = 4.71, 95% CI: 3.39-6.53), HPV58 infection (aOR = 2.29, 95% CI: 1.41-3.73) and PAHs high exposure (aOR = 2.57, 95% CI: 1.82-3.62) increased the risk of CIN2/3, showing an increasing trend (p < 0.001) with the severity of cervical lesions. Compared to Q1 (<0.06 µmol/molCr) levels of 1-OHP, women with Q4 (>0.11 µmol/molCr) had a higher risk for CIN2/3 (aOR = 7.68, 95% CI: 4.83-12.22). Additionally, we observed that there was a synergic effect between high exposure to PAHs and HR-HPV infection in CIN2/3. Furthermore, the results from the generalized multifactor dimensionality reduction model showed that there were joint interactions of PAHs, HPV16, HPV58 and HPV52 on the risk of CIN2/3. Our study revealed that high exposure to PAHs could increase the risk for CIN, and it posed stronger risk when combined with HR-HPV infection.

Pyrene metabolites by bacterium enhancing cell division of green alga Selenastrum capricornutum.

Collaborations between multiple microbial species are important for understanding natural clearance and ecological effects of toxic organic contaminants in the environment. However, the interactions between different species in the transformation and degradation of contaminants remain to address. In this study, the effects of pyrene and its bacterial metabolites on the algal growth (Selenastrum capricornutum) were examined. The specific growth rate of algal cells incubated with bacterial pyrene metabolites (1.18 d-1) was highest among all treatment, followed by the controls (1.07 d-1), treated with pyrene-free bacterial metabolites (1.04 d-1) and those treated with pyrene (0.55 d-1). G1 phase is the key growth phase for the cells to synthesize biomolecules for subsequent cell division in the cell cycle. Approximately 76.9% of the cells treated with bacterial pyrene metabolites were at the G1 phase and significantly lower than those with the controls (85.3%), pyrene-free bacterial metabolites (85.5%) and pyrene treatment (92.5%). Transcriptomic analysis of algae showed that the expression of 47 ribosomal unigenes was down-regulated by 5 mg L-1 of pyrene, while 308 unigenes related to the preparation of cell division (DNA replication and protein synthesis) were up-regulated by bacterial pyrene metabolites. It indicated that basal metabolism associated with the growth and proliferation of algal cells could be significantly promoted by bacterial pyrene metabolites. Overall, this study suggests a close relationship between algae and bacteria in the transformation and ecological effects of toxic contaminants.

Polycyclic aromatic hydrocarbons exposure and hematotoxicity in occupational population: A two-year follow-up study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and occupational pollutants. To date, the effect and mechanism by which PAHs exposure impaired hematopoietic system remains unclear. METHODS: We examined the capability of PAHs to disrupt hematopoiesis in a study of 639 male participants in China by measuring complete blood counts (CBC) in 2013 and 2014. Gas chromatography-mass spectrometry (GC/MS) method was used to measure airborne levels of PAHs and benzene. We measured 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (SPMA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urinary by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method. RESULTS: We found decreased dose-response of white blood cells, eosinophils, monocytes and lymphocytes with increased PAHs exposure in two consecutive years. We did not find association between benzene with CBC in our study. After stratification analysis by smoking status, the findings were highly consistent. White blood cells, monocytes and red blood cell counts were decreased in high urinary 8-OHdG group. CONCLUSIONS: Our study showed that PAHs could impair the hematopoietic system independently, and oxidative stress might play an important role in potential hematotoxicity.

Expression levels of circulating microRNAs-126, -155, and -145 in Mexican women exposed to polycyclic aromatic hydrocarbons through biomass fuel use.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been considered a risk determinant for the development of cardiovascular diseases (CVD). Therefore, the aim of this study was to assess expression levels of vascular-related miRNAs, miR-126, miR-155, and miR-145, in plasma from women (aged 19-81 years) exposed (n = 100) and non-exposed (n = 20) to PAHs via biomass combustion smoke.1-hydroxypyrene (1-OHP) was determined in urine as a biomarker of exposure to PAHs using high-resolution liquid chromatography. Plasma expression levels of proposed miRNAs were determined by quantitative real-time PCR. Additionally, traditional risk factors (age, blood pressure, serum lipid profile, blood glucose, and among others) associated with CVD were evaluated. Urinary 1-OHP concentrations and plasma expression levels of miR-126 and miR-155 were significantly higher (P < 0.05) in women using wood as a fuel source in their homes (indoor) compared to women from the reference group (non-exposed to biomass smoke). Besides, multivariate linear regression analyses revealed that miR-126[ß = 0.61; 95% confidence interval (0.32-0.90)] and miR-155 [ß = 0.45; 95% confidence interval (0.13-0.84)] expression levels were significantly associated with urinary 1-OHP concentrations after being adjusted by traditional risk factors (P < 0.05). In contrast, no significant relationship was found between miR-145 and urinary 1-OHP levels. Furthermore, miRNAs assessed in this investigation are associated with CVD events. Consequently, actions to reduce exposure to PAHs in the evaluated population are warranted. Environ. Mol. Mutagen. 60:546-558, 2019. © 2019 Wiley Periodicals, Inc.

Gestational 1-nitropyrene exposure causes fetal growth restriction through disturbing placental vascularity and proliferation.

1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is best known for its mutagenicity and carcinogenicity. In this study, we evaluated the effects of 1-NP exposure in different gestational stages on the pregnant outcomes. Pregnant mice were administered with 1-NP by gavage daily in early (GD1-GD6), middle (GD7-GD12) or late pregnancy (GD13-GD17), respectively. We found that gestational 1-NP exposure had no effect on implantation sites per litter, preterm delivery and fetal death. Interestingly, mice exposed to 1-NP in late pregnancy showed a significant reduction in fetal weight and crown-rump length. Correspondingly, placental weight and diameter were markedly reduced in dams exposed to 1-NP in late pregnancy. Additional experiment showed maternal 1-NP exposure in late pregnancy reduced blood sinusoid area of placental labyrinthine region in a dose-dependent manner. Although gestational 1-NP exposure had little effect on placental cell apoptosis, as determined by the TUNEL assay, the rate of Ki67-positive cell, a marker of cell proliferation, was reduced in placental labyrinthine region of mice exposed to 1-NP in late pregnancy. These findings provide evidence that gestational 1-NP exposure induces fetal growth restriction in a stage-dependent manner. Placenta is a toxic target in the process of 1-NP-induced fetal growth restriction.

S phase arrest in lymphocytes induced by urinary 1-hydroxypyrene and alcohol drinking in coke oven workers.

Arrest of the cell cycle after DNA damage is believed to promote DNA repair. We aim to investigate the main factors affecting cell cycle arrest of lymphocytes in coke oven workers. A total of 600 workers were included in this study, and their urinary levels of four polycyclic aromatic hydrocarbons (PAH) metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and cell cycle distribution were determined. Urinary PAH metabolites were significantly increased in coke oven workers ( p < 0.01). It was found that only urinary 2-hydroxynaphthalene and 1-hydroxypyrene showed significant positive linear dose-response effects on 8-OHdG in this study population ( ptrend = 0.025 and 0.017, respectively). The dose-response effect was also observed for smoking and drinking on 8-OHdG ( ptrend < 0.001 and 0.034, respectively). Multivariate logistic regression analysis revealed that high levels of urinary 1-hydroxypyrene were associated with a significantly increased risk of S phase arrest (odds ratio (OR) = 1.32, p = 0.03), so as heavy alcohol drinking (OR = 1.31, p = 0.02). Drinking can significantly modify the effects of urinary 1-hydroxypyrene on S phase arrest, during co-exposure to both heavy drinking and median or high 1-hydroxypyrene levels (OR = 3.31, 95% confidence interval (CI) = 1.21-7.63 and OR = 2.56, 95% CI = 1.08-6.06, respectively). Our findings demonstrate that coke oven workers with heavy drinking will cause S phase arrest so as to repair more serious DNA damage.

[Combined effects of 1-nitropyrene and 1,2-naphthoquinone on cytotoxicity and DNA damage in A549 cells].

Using human lung epithelial A549 cells, viability was measured by MTT assay after treated with 1-nitropyrene (1-NP); lactate dehydrogenase (LDH) leakage was determined to evaluate the cellular membrane injury; DNA damage was detected with comet assay; reactive oxygen species (ROS) generation was measured with fluorescent probe. The combined toxic effects of 1-NP and 1,2-naphthoquinone (1,2-NQ) on A549 were also evaluated. 1-NP caused a significantly concentration-dependent and time-dependent viability decrease. The LC50 for 24 h and 48 h were 5.2 µmol x L(-1) and 2.8 µmol x L(-1), respectively. DNA damage and intracellular ROS levels were also increased significantly through a dose-dependent manner after exposure to 1-NP. The LDH leakage were not significantly changed. Compared with the groups treated with 1-NP alone, the viability and LDH leakage was not changed significantly in combined-treated groups with 1-NP and 1,2-NQ. However, the DNA damage and ROS levels were significantly reduced in the combined-treated groups compared with the groups treated with 1-NP alone. These results suggest that 1-NP may mediated the genotoxic and cytotoxic effects through ROS generation, and pretreatment with 1,2-NQ, may inhibit the ROS generation induced by 1-NP, and thereby reducing the DNA damage in A549 cells.

Nutritional status of Carcinus maenas (Crustacea: Decapoda) influences susceptibility to contaminant exposure.

Using the shore crab Carcinus maenas as a model, this study tested the hypothesis that nutritional status influences susceptibility of adult crabs (>60mm carapace width (CW)) to environmental contamination. In the laboratory, crabs were either starved, given a restricted diet (fed on alternate days) or fully fed (fed each day). In addition, crabs under each feeding regime were exposed to a sublethal concentration (200microgl(-1)) of pyrene (PYR) as a model organic (PAH (polyaromatic hydrocarbon)) contaminant. Various physiological end points were measured after 7 and 14 days. Results indicated that adult shore crab physiology was relatively robust to short-term (7 days) nutritional changes as multivariate analysis (ANOSIM) showed no significant difference in shore crab physiological condition between control and pyrene-exposed crabs, irrespective of dietary feeding regime [Global R=0.018, P (%)=19.2]. After 14 days, however, starved crabs showed significant impacts to physiological condition (as revealed by multivariate analysis) [Global R=0.134, P (%)=0.1], [R=0.209, P (%)=0.1]; starved individuals had significantly lower antioxidant status (F(2,48)=5.35, P<0.01) compared to crabs under both types of feeding regime. Exposure to pyrene resulted in significantly elevated pyrene metabolite concentrations in the urine at 7 and 14 days compared with control individuals (P<0.001), validating contaminant bioavailability, and this was found for all dietary treatments. Also, exposed crabs had significantly increased protein levels (proteinuria) than controls (P<0.001) in their urine after 7 and 14 days, irrespective of dietary regime. After 7 days, pyrene-exposed crabs showed significantly increased antioxidant status (P<0.001) and cellular functioning (increased cellular viability and decreased phagocytosis) (P<0.001) compared to control crabs; however, after 14 days, antioxidant status (P<0.01) and cellular viability (P<0.001) were significantly decreased in pyrene-exposed compared to unexposed crabs. Results indicate that differences in nutritional status of adult crabs result in shore crabs being robust to short-term sublethal (7 days) pyrene exposure. Susceptibility to contaminant exposure, however, was measured after prolonged exposure (14 days) as indicated by reduced ability to combat oxidative stress. These results indicate that ecotoxicological studies need to take into account the nutritional state of the test organism to achieve the full assessment of contaminant impact. In addition, the results highlight that subtle seasonal biotic features of an organism can influence biomarker responses, and these need to be considered when interpreting field data and during the routine application of biological-effects tools in environmental monitoring.

Levels of 1-hydroxypyrene, symptoms and immunologic markers in vulcanization workers in the southern Sweden rubber industries.

OBJECTIVES: The aim of this study was to determine urinary 1-hydroxypyrene (1-HP) levels in contemporary Swedish vulcanization workers and in controls. These levels were used as an index substance for vulcanization fumes, as well as a biomarker for polycyclic aromatic hydrocarbons (PAHs). The risk of symptoms and changed levels of immunologic markers were investigated in relation to the 1-HP levels. METHODS: Included in the study were 163 exposed workers and 106 controls. Medical and occupational histories were obtained by structured interviews. Symptoms were recorded and immunologic markers analysed in blood by routine analysis methods. Levels of 1-HP were determined by liquid chromatography and fluorescence detection. RESULTS: The highest levels of 1-HP were found among exposed workers using injection and compression vulcanization and lower levels were found among exposed workers vulcanizing with salt bath, hot air, microwaves or fluid-bed. Compared to controls, exposed workers had increased risks of eye symptoms, nosebleeds, burning and dry throat, hoarseness, severe dry cough, nausea and headache. Furthermore, exposed workers had elevated levels of neutrophils and total IgG (immunoglobulin subclass G). However, only for severe dry cough an evident exposure-response relationship with urinary 1-HP levels was found. CONCLUSIONS: This work clearly shows increased levels of urinary 1-HP in Swedish vulcanization workers. Furthermore, it demonstrates an increased risk of several symptoms and elevated levels of some immunologic markers in these workers. However, no obvious exposure-response relationships were found.

[In vivo mutagenicity of the carcinogenic 1-nitropyrene. A model of a potential asbestos exposure]. / A karcinogén 1-nitropirén in vivo mutagenitása, egy potenciális azbesztexpozíció modellje.

The environmental carcinogen 1-nitropyrene was orally and intraperitoneally administered to rats in a single dose of 30 mmol/kg. Mutagenicity of excreted urine was tested in Salmonella typhimurium TA 98 and 100 strains. The mutagenic pattern of urine in case of oral exposure proved to be completely different as compared to the intraperitoneal administration. Frame-shift mutagen(s) was/were detected only after enzymatic deconjugation of sulphate or glucuronide metabolites within the first 24 h. Base-pair substitution-type mutagenicity was only detected in the urine samples collected after intraperitoneal treatment. Since environmental asbestos exposure involves carcinogenic effects of adsorbed polycyclic aromatic hydrocarbons, this animal model provides a useful tool for testing fiber-associated nitroarenes, in both mechanistic and risk assessment studies.

A non-destructive assessment of the exposure of crabs to PAH using ELISA analyses of their urine and haemolymph.

Urine and haemolymph can be repeatedly sampled from crabs with no (or limited) damage to the organism. Their analysis offers a measure of the animals' exposure to biologically available contaminants. Shore crabs (Carcinus maenas) were exposed to the PAHs phenanthrene and pyrene at concentrations ranging from 20 to 200 microg l(-1). After 48 h, urine and haemolymph samples were taken and analysed using ELISA and UV-fluorescence spectrophotometry. High correlations were recorded between the two sets of results from the urine analyses (r2 = 0.83 for phenanthrene and r2 = 0.88 for pyrene). Contaminant concentrations were much lower in haemolymph than in the urine. Analyses of urine taken from crabs collected from clean and contaminated sites confirm the suitability of these analyses for environmentally exposed organisms. Again, a good correlation was recorded between the ELISA and spectrofluorimetric analysis (r2 = 0.83). In this instance, difficulties were experienced with haemolymph analyses owing to a lack of sensitivity.

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a study in underground mining.

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil shale mine in Estonia were compared with surface workers. Personal exposures to particle-associated 1-nitropyrene (NP) were some eight times higher underground than on the surface. Underground miners were also occupationally exposed to benzene and polycyclic aromatic hydrocarbons, as indicated by excretion of urinary metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA adducts were detected in the white blood cells of underground workers, suggesting higher exposure to nitroso-compounds. However, no differences between underground and surface workers were observed in the levels of other bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results.

Alterations of motor nerve functions in animals exposed to motorcycle exhaust.

The effect of motorcycle exhaust (ME) on the motor nerve was studied using animals exposed to the exhaust by inhalation, intratracheal, or intraperitoneal administration of ME particulate (MEP). A 4-wk ME inhalation and intratracheal instillation of MEP for 1 d in rats or intraperitoneal administration of MEP (0.5 g/kg/d for 1 d and 0.1 g/kg/d for 2 d) in mice significantly decreased both rota-rod performance and motor nerve conduction velocity. The effect of some polycyclic aromatic hydrocarbons on the motor nerve was also investigated. Treatment with benzo[a]pyrene (0.05 and 0.1 g/kg/d for 3 d), but not pyrene (0.1 g/kg/d for 3 d), resulted in significant decrease of motor nerve conduction velocity in mice. Moreover, the Na(+),K(+)-ATPase activities of sciatic nerves isolated from ME-, MEP-, or benzo[a]pyrene-exposed animals were decreased. Treatment with pyrene did not markedly affect the Na(+),K(+)-ATPase activity of sciatic nerve. The rats exposed to ME for 4 wk showed increases in blood and sciatic nerve manganese levels. Results indicate that motorcycle exhaust produces adverse effects on the motor nerve, which is associated with a fall in nerve Na(+),K(+)-ATPase activity.

Urinary 1-hydroxypyrene as a biomarker of internal dose of polycyclic aromatic hydrocarbons in carbon black workers.

In this study, a total of 30 workers were selected, including eight wet pelletizing workers and 22 packaging workers. For all selected workers, urine samples were collected on the first day pre-shift, first day post-shift and fifth day post-shift, and their urinary 1-hydroxylpyrene levels (1-OHP) were determined (denoted as BM1pre, BM1post and BM5post, respectively). Personal respiratory exposures, including both inhalable particle-bound PAHs (Cinh) and gaseous PAHs (Cgas), together with dermal exposure to particle-bound PAHs (Cskin) were measured. Personal background information, including age, sex and smoking habit, was carefully registered. Pyrene exposure was statistically significantly correlated with exposure to PAHs and carcinogenic PAHs. Multiple linear regression analysis results showed that the BM1post values could not be explained by workers' exposures. For BM5post in packaging workers, both the regression model (R2 = 0.73) and the regression coefficients for Cgas, Cinh and Cskin were statistically significant (P < 0.05). For pelletizing workers, the R2 value was higher but was not statistically significant because of the smaller number of workers. The resultant regression coefficients for 'sex', 'smoking habit' and 'age' were statistically insignificant (P >> 0.05), which could be because these variables made relatively small contributions to BM5post. In conclusion, this study suggests BM5post could be a suitable indicator for PAH exposures of carbon black workers, on the condition that both respiratory (including gaseous PAHs and particle-bound PAHs) and dermal exposures have been assessed.

Effects of sludge-amendment on mineralization of pyrene and microorganisms in sludge and soil.

Hydrophobic contaminants sorb to sludge in wastewater treatment plants and enter the soil environment when the sludge is applied to agricultural fields. The mineralization of pyrene was examined in soil, in sludge mixed homogeneously into soil, and in sludge-soil systems containing a lump of sludge. Sludge-amendment enhanced the mineralization of pyrene in the soil compared to soil without sludge, and the most extensive mineralization was observed when the sludge was kept in a lump. The number of protozoa, heterotrophic bacteria and pyrene-mineralizing bacteria was much higher in the sludge compared to the soil. The amendment of sludge did not affect the number of protozoa and bacteria in the surrounding soil, which indicated that organic contaminants in the sludge had a little effect on the number of protozoa and bacteria in the surrounding soil.

DNA strand breaks, oxidative damage, and 1-OH pyrene in roofers with coal-tar pitch dust and/or asphalt fume exposure.

OBJECTIVE: To determine the potential for asphalt fume exposure to increase DNA damage, we conducted a cross-sectional study of roofers involved in the application of roofing asphalt. METHODS: DNA strand breaks and the ratio of 8-hydroxydeoxyguanosine (8-OHdG) to 2-deoxyguanosine (dG) were measured in peripheral blood leukocytes of roofers. In addition, urinary excretion of 8-OHdG and 8-epi-prostaglandin F2alpha (8-epi-PGF) was also measured. The study population consisted of 26 roofers exposed to roofing asphalt and 15 construction workers not exposed to asphalt during the past 5 years. A subset of asphalt roofers (n = 19) was exposed to coal-tar pitch dust (coal tar) during removal of existing roofs prior to applying hot asphalt. Personal air monitoring was performed for one work-week to measure exposure to total particulates, benzene-soluble fraction of total particulates, and polycyclic aromatic compounds (PACs). Urinary 1-OH-pyrene levels were measured as an internal biomarker of PAC exposure. RESULTS: Full-shift breathing zone measurements for total particulates, benzene-solubles and PACs were significantly higher for coal-tar exposed workers than for roofers not exposed to coal tar. Similarly, urinary 1-OH-pyrene levels were higher in coal-tar exposed roofers than roofers not exposed to coal tar. Total particulates or benzene-soluble fractions were not associated with urinary 1-OH-pyrene, but PAC exposure was highly correlated with urinary 1-OH-pyrene. When stratified by 1-OH-pyrene excretion, DNA strand breaks increased in a dose-dependent manner, and leukocyte 8-OHdG/dG decreased in a dose-dependent manner. Significant changes in DNA damage appeared to be linked to PACs from coal-tar exposure, although asphalt fume alone was associated with a small but significant increase in urinary 1-OH-pyrene and DNA strand breaks. CONCLUSIONS: Results are consistent with previous reports that asphalt or coal-tar exposure can cause DNA damage. Urinary 8-epi-PGF remained relatively constant during the week for virtually all subjects, regardless of exposure indicating that neither asphalt nor coal-tar exposure induces an overt oxidative stress. A small, but statistically significant increase in 8OHdG was evident in end-of-week urine samples compared with start-of-week urine samples in roofers exposed to coal-tar. The increase in urinary 8OHdG coupled with the decrease in leukocyte 8-OHdG/dG, suggests that coal-tar exposure induces protective or repair mechanisms that result in reduced levels of steady-state oxidative-DNA damage.

Seasonal effect on airborne pyrene, urinary 1-hydroxypyrene, and benzo(a)pyrene diol epoxide-hemoglobin adducts in the general population.

Exposure to airborne polycyclic aromatic hydrocarbons (PAHs) in 65 employees (40 sampled both in summer and winter, 15 sampled in summer only, and 10 sampled in winter only) with no occupational exposure to PAHs was assessed by measuring: personal exposure to pyrene, urinary excretion of 1-hydroxypyrene (1-OHP), and benzo(a)pyrene diol epoxide adducts to hemoglobin (BPDE-Hb). Overall, office employees were exposed to significantly higher levels of pyrene in winter (4.54 +/- 2.35 ng/m3, mean +/- SD) than in summer (1.67 +/- 1.92 ng/m3, mean +/- SD; P < 0.001), but no such seasonal variability was observed in 1-OHP excretion. Tobacco smoking was the major determinant of 1-OHP excretion. BPDE-Hb adducts were measured by gas chromatography-mass spectrometry as benzo(a)pyrene tetrols (BPT) released from adducted hemoglobin. In the 65 employees analyzed, mean BPT levels +/- SD were higher in winter (0.14 +/- 0.38 fmol/mg Hb) than summer (0.031 +/- 0.022 fmol/mg Hb). This difference was not statistically significant, probably because of the small proportion of subjects with detectable adducts (11% in summer and 16% in winter). BPDE-Hb adducts were not significantly associated with sex, age, diet, smoking habits, or with pyrene levels and 1-OHP excretion. This is the first report providing reference BPDE-Hb adduct values for the general population not occupationally exposed to environmental PAHs and shows a tendency to seasonal variability, with higher BPT levels in winter when environmental PAHs are also high.