Oxidative stress of office workers relevant to tobacco smoking and inner air quality.

Studies have used 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker to detect systemic oxidative DNA damage associated with oxidative stress. However, studies on the association between exposure to tobacco smoking and urinary 8-OHdgG give inconsistent results. Limited studies have estimated the oxidative stress among office workers. This study assessed the association between urinary 8-OHdG and cotinine for office workers.  Workers (389) including smokers, ex-smokers and non-smokers from 87 offices at high-rise buildings in Taipei participated in this study with informed consent. Each participant completed a questionnaire and provided a spot urine specimen at the end of work day for measuring urinary 8-OHdG and cotinine. The carbon dioxide (CO2) levels in workers' offices were also measured. The questionnaire reported socio-demographic characteristics, life styles and allergic history. The urinary 8-OHdG level increased with the cotinine level among participants (Spearmans' rho = 0.543, p < 0.001). The mean of urinary 8-OHdG and cotinine was 5.81 ± 3.53 µg/g creatinine and 3.76 ± 4.06 µg/g creatinine, respectively. Comparing with non-smokers, the adjusted odds ratio (OR) of having urinary 8-OHdG greater than the median level of 4.99 µg/g creatinine was 5.30 (95% confidence intervals (CI) = 1.30-21.5) for current smokers and 0.91 (95% CI = 0.34-2.43) for former smokers. We also found workers exposed to 1,000 ppm of CO2 at offices had an adjusted OR of 4.28 (95% CI = 1.12-16.4) to have urinary 8-OHdG greater than 4.99 µg/g creatinine, compared to those exposed to indoor CO2 under 600 ppm. In conclusion, urinary 8-OHdG could represent a suitable marker for measuring smoking and CO2 exposure for office workers.

Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma.

Fibroblast growth factor (FGF)-9 belongs to the FGF family which modulate cell proliferation, differentiation, and motility. Benzo(a)pyrene is a polycyclic aromatic hydrocarbon (PAH) and ubiquitous environmental carcinogen present in automobile exhaust, cigarette smoke, and foods. The major purposes of this study were to explore the roles of FGF-9 in the benzo(a)pyrene-induced lung cancer invasion in vitro and the metastatic development of lung adenocarcinoma in human. The data of RT-PCR analysis indicated that treatments of human lung adenocarcinoma CL5 cells with benzo(a)pyrene and a PAH mixture motorcycle exhaust particulate (MEP) extracts increased FGF-9 mRNA expression. The increased expression was blocked by cotreatments with a p38 mitogen-activated protein kinase inhibitor SB202190 and an extracellular signal-regulated kinase inhibitor PD98059. The results of immunoblot analysis and Matrigel assay showed that benzo(a)pyrene and MEP extracts produced a concomitant induction of FGF-9 protein and invasive ability of CL5 cells. The benzo(a)pyrene- and MEP-induced invasion was suppressed by FGF-9 neutralizing antibodies. The results of immunohistochemistry analysis of human lung adenocarcinoma specimens showed that FGF-9 protein was detected in the adenocarcinoma cells but not in normal epithelium. FGF-9 staining intensity was positively correlated with status of disease and degree of lymph node metastasis in these lung adenocarcinomas. These present findings suggest that FGF-9 has potential roles in benzo(a)pyrene-induced CL5 cell invasion and human lung adenocarcinoma metastasis.

Serum dioxin levels in residents living in the vicinity of municipal waste incinerators in Taiwan.

This study used data obtained from the Taiwan Environmental Protection Administration to measure the dioxin exposure and the body burden for residents living in the vicinity of 19 municipal waste incinerators (MWIs). A survey was conducted in 1999-2003 for the residents. Approximately 16 ambient air samples and a 60-ml blood samples of 84 to 92 residents aged 18-65 yr were collected randomly in four zones (A, B, C, D) for each MWI site based on the atmospheric dispersion model (ADM). Zone A was defined with the highest pollution level, followed by zones B and C, and zone D (background level). Congeners of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined for each sample. We summarized the PCDD/Fs levels in air samples and serum specimens by zone for these 19 sites. The mean ambient levels of PCDD/Fs fitted the ADM, the highest from zone A and the lowest from zone D (2.74 vs. 0.13 pg I-TEQ/Nm3). However, the mean serum concentration in zones A was not distinct from that in zones D (18.7 vs. 19.0 pg WHO-TEQ/g lipid). The age-specific average serum concentration increased from 13.27 pg WHO-TEQ/g in 18- to 25-yr-old subjects to 23.46 pg WHO-TEQ/g lipid in 56- to 65-yr-old subjects. In conclusion, the serum PCDD/Fs levels among residents did not adhere to the dispersion model for incineration emissions. The dose-response of serum PCDD/Fs by age suggests that the body burden of the chemicals is mainly associated with other sources instead of with inhalation.

Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine and indoor air pollution among non-smoking office employees.

This study investigated whether urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, was associated with indoor air quality for non-smokers in high-rise building offices. With informed consents, urine samples from 344 non-smoking employees in 86 offices were collected to determine 8-OHdG concentrations. The concentrations of carbon dioxide (CO(2)) and total volatile organic compounds (TVOCs) in each office and outside of the building were simultaneously measured for eight office hours. The average workday difference between indoor and outdoor CO(2) concentrations (dCO(2)) was used as a surrogate measure of the ventilation efficiency for each office unit. The CO(2) levels in the offices ranged 467-2810ppm with a mean of 1170ppm, or 2.7 times higher than that in the outside air. The average urinary 8-OHdG levels among employees increased from 3.10 micro g/g creatinine, for those at the lowest tertile levels of both dCO(2) and TVOCs, to 6.27 micro g/g creatinine, for those at the highest tertile levels. Multivariate logistic regression analysis showed that the risk of having the urinary 8-OHdG level of greater than the median, 4.53 micro g/g creatinine, for participants was increased significantly at the highest tertile dCO(2) level of >680ppm (odds ratio (OR)=3.37, 95% confidence interval (CI)=1.20-9.46). The effect was significant at the middle tertile TVOCs level of 114-360ppb (OR=2.62, 95% CI=1.43-4.79), but not at the highest tertile. Inadequate ventilation in office increases the risk of building-related oxidative stress in non-smoking employees.

Oxidative stress associated with indoor air pollution and sick building syndrome-related symptoms among office workers in Taiwan.

This study investigated whether sick building syndrome (SBS) complaints and indoor air pollution for office workers are associated with oxidative stress indicated by urinary 8-hydroxydeoxyguanosine (8-OHdG). With informed consent, 389 employees in 87 government offices of 8 high-rise buildings in Taipei city completed self-reported questionnaires on SBS complaints at work in the past month. Urinary 8-OHdG was determined for each study participant and on-site air pollutants were measured for each office in both indoor and outdoor air. The results showed that urinary 8-OHdG had significant associations with volatile organic compounds and carbon dioxide levels in offices, and with urinary cotinine levels. The mean urinary 8-OHdG level was also significantly higher in participants with SBS symptoms than in those without such complaints (6.16 vs. 5.45 mug/g creatinine, p = .047). The mean 8-OHdG increased as the number of SBS symptoms increased. The multivariate logistic regression analyses showed that the adjusted odds ratios (OR) in relation to micrograms per gram creatinine increase in 8-OHdG were statistically significant for eye dryness (1.12), upper respiratory syndrome (1.17) with particularly nose itching (1.25), sneezing (1.51), dry throat (1.21), skin dryness (1.31), and dizziness (1.19). This study indicates that the 8-OHdG level was significantly associated with SBS complaints after controlling for air pollution and smoking. Whether the 8-OHdG can be used as an effective predictor for SBS symptoms deserves further study.

Measurement of benzylmercapturic acid in human urine by liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry.

A method based on liquid chromatography (reversed-phase)-electrospray (negative) ionization-tandem triple quadrupole mass spectrometry [LC-ESI(-)-MS-MS], in the multiple reaction monitoring mode, was developed for determination of urinary benzylmercapturic acid (BMA). Isotope dilution through introduction of (13)C(6)-labeled BMA was employed as an internal standard, achieving intra- and interrun precision ranges of 2.32-2.95% and 2.24-4.97%, respectively. The calibration curve obtained with BMA-spiked blank human urine was linear from 0.5-120.0 microg/L; the correlation coefficient of the calibration curve was 0.999. The method limit of quantification was 0.5 microg/L; mean BMA recovery was 97.56%. The analytical method was used to analyze urine samples collected from workers involved in the manufacture of adhesive tape who had been exposed to toluene. The method appears to provide sensitive, specific, and reliable testing for urinary BMA to determine occupational exposure to toluene.

Evaluation of the effects of various gas chromatographic parameters on haloacetic acids disinfection by-products analysis.

Thermal decomposition of the analytes during the analysis is a problem for haloacetic acids (HAAs). We evaluated the effect of GC injection port temperature and the amount of trace water in the sample on the HAAs' analysis. For three brominated HAAs, the variation in intensity due to the change of injection port temperature was significant. The largest variation observed was tribromoacetic acid methyl ester (from 3.2 to 1 for injection port temperature changing from 170 degrees C to 250 degrees C). Tribromoacetic acid methyl ester partially decomposed to dibromoacetic acid and to tribromomethane in a competitive way. At a low injection port temperature, tribromomethane formation was preferred, but at a high injection port temperature, the debrominated methyl ester formation dominated. Water contained in the sample may accelerate the hydrolysis process of the esters in the injection port, and this effect was also the greatest for the brominated trihaloacetic acids. Direct injection of underivatized HAAs into the GC/MS indicated that brominated HAAs can be nearly quantitatively thermal decomposed to the corresponding halomethanes.

DNA single strand breaks in peripheral lymphocytes associated with urinary thiodiglycolic acid levels in polyvinyl chloride workers.

The association between vinyl chloride monomer (VCM) exposure and DNA damage has been established. However, the relationship between individual exposure and DNA single strand breaks was limited. Since environmental monitoring may not reflect the actual exposure, a useful marker of exposure is needed to assess the individual exposure. In our previous study, we have found a high correlation between air VCM level and urinary thiodiglycolic acid (TdGA) at the commencement of the next shift. Here, we further used comet assay to evaluate the relationship between urinary TdGA levels and DNA single strand breaks in polyvinyl chloride monomer (PVC) workers. Urinary TdGA levels (n=26) at the commencement of the following shift were analyzed. Ten of the 26 workers also had personal air sampling for air VCM exposure. Questionnaires were administered to obtain epidemiological information including detailed history of occupation and lifestyles. Workers experiencing air VCM level greater than 5 ppm had higher tail moment and tail intensity (%) than those experiencing VCM exposure between 1 and 5, or <1 ppm, respectively (P < 0.05). The results also revealed that level of DNA single strand breaks, including tail moment and tail intensity, were increased with urinary TdGA level. The dose-response relationship of urinary TdGA level and DNA single strand breaks was particularly significant among the workers with 4 mg/g Cr of urinary TdGA level, which is equivalent to 5 ppm air VCM level. We concluded that air VCM exposure greater than 5 ppm could induce DNA damage. Further sensitive assay should be developed for the diction of DNA damage when air VCM exposure below 5 ppm.

Health risk assessment on residents exposed to chlorinated hydrocarbons contaminated in groundwater of a hazardous waste site.

We conducted this study to estimate residents' chronic hazard and carcinogenic risk in a groundwater-contaminated community after on-site remediation in Taiwan during 1999-2000. We followed guidelines for assessing hazardous waste sites of the U.S. Environmental Protection Agency (EPA) and used empirically measured contaminant levels and exposure parameters to perform health risk assessment on seven chlorinated hydrocarbons. We measured groundwater concentrations of vinyl chloride, tetrachloroethylene, trichloroethylene, 1,1-dichloroethylene, 1,1,1-trichloroethane, cis-1,2-dichloroethylene, and 1,1-dichloroethane in 49 off-site residential wells by gas chromatography/mass spectrometry. Exposure parameters were mainly derived from our field survey of 382 residents, and partially from U.S. EPA default values. Total exposure dose estimation included routes of inhalation during showering and dermal absorption of showers and other activities involved with hand-water contacts. The ingestion route of water was not included because most residents drank boiled water with negligible contaminants. We calculated a hazard index (HI) for all seven chlorinated hydrocarbons and carcinogenic risks for known human carcinogen of vinyl chloride and probable human carcinogens of tetrachloroethylene and trichloroethylene, which had the same target organ, the liver. The HI values for reasonable maximal exposure (RME) and average exposure were 14.3 and 0.2, respectively. The cancer risks based on RME and average exposure (in parentheses) for vinyl chloride, tetrachloroethylene, and trichloroethylene were 8.4 x 10(-6) (7.3 x 10(-9)), 1.9 x 10(-4) (1.3 x 10(-7)), and 1.4 x 10(-4) (1.2 x 10(-6)), respectively. We applied Monte Carlo simulations to the sensitivity analysis, which showed that the contaminant levels, exposure duration, and time for showers were major determinants of health risks. We concluded that the contaminated groundwater was still unsafe for use even after the contaminated site underwent remediation by extraction and treatment in 1997.

Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.