Exposure to indoor background radiation and urinary concentrations of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage

We investigated whether exposure to indoor [gamma]-radiation and radon might be associated with enough free radical formation to increase urinary concentrations of 8-hydroxydeoxyguanosine (8-OHdG), a sensitive marker of DNA damage, due to a hydroxyl radical attack at the C8 of guanine. Indoor radon and [gamma]-radiation levels were measured in 32 dwellings for 6 months by solid-state nuclear track detectors and thermoluminescent dosimeters, respectively. Urine samples for 8-OHdG determinations were obtained from 63 healthy adult subjects living in the measured dwellings. An overall tendency toward increasing levels of 8-OHdG with increasing levels of radon and [gamma]-radiation was seen in the females, presumably due to their estimated longer occupancy in the dwellings measured. Different models were considered for females, with the steepest slopes obtained for [gamma]-radiation with a coefficient of 0.500 (log nmol/l of 8-OHdG for each unit increase of [gamma]-radiation on a log scale) (p<0.01), and increasing to 0.632 (p = 0.035), but with larger variance, when radon was included in the model. In conclusion, there seems to be an effect of indoor radioactivity on the urinary excretion of 8-OHdG for females, who are estimated to have a higher occupancy in the dwellings measured than for males, for whom occupational and other agents may also influence 8-OHdG excretion. ree radicals; [gamma]-radiation; radon.     

Exposure to benzene and urinary concentrations of 8-hydroxydeoxyguanosine, a biological marker of oxidative damage to DNA.

OBJECTIVES--Benzene is an established animal and human carcinogen. The mechanism of benzene toxicity, particularly its leukaemogenic effect, is not fully understood. The modified base 8-hydroxy-deoxyguanosine (8-OHdG) is a sensitive marker of the DNA damage due to hydroxyl radical attack at the C8 of guanine. This damage, if left unrepaired, has been proposed to contribute to mutagenicity and cancer promotion. We conducted this biomonitoring study with the aim of evaluating the association between excretion of 8-OHdG and level of exposure to benzene and other aromatic compounds among occupationally exposed people. METHODS--A random sample of 65 filling station attendants from Rome, Italy was studied for personal exposure to benzene, toluene, and xylenes, and excretion of 8-OHdG. Information about age, length of employment, smoking habits, and diagnostic exposure to x rays was collected by questionnaire. An average yearly level of exposure to benzene and methylbenzenes was calculated for each filling station attendant on the basis of about seven repeated personal samples collected during one year. A spot sample of 20 ml of urine was collected from each worker. Concentrations of 8-OHdG were determined by high performance liquid chromatography (HPLC) with coupled columns. RESULTS--A mean (SD) concentration of 1.36 (0.49) mumol of 8-OHdG/mol of creatinine was measured. A significant correlation was found between urinary 8-OHdG and exposure to benzene (r = 0.34). In a multiple regression analysis relating the concentration of urinary 8-OHdG with the age, length of employment, smoking, diagnostic exposure to x rays and personal exposure to benzene, an increase of 0.15 mumol/mol creatinine in urinary 8-OHdG/unit increase in the natural logarithm of the average yearly benzene concentration was estimated. CONCLUSION--This study shows a dose-response effect between personal exposure to benzene and urinary 8-OHdG concentration; further studies are needed to clarify the biological significance of 8-OHdG as a marker of cancer risk.     

Urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to ethylbenzene

This study assessed the relationships between ethylbenzene exposure and levels of 8-hydroxydeoxyguanosine (8-OHdG) among spray painters. Sixty-four male workers employed at a large shipyard were recruited for this investigation. Fifteen spray painters exposed to paint, together with two non-exposed groups, namely 19 sandblasting workers and 30 office staffs were selected as the subjects. Personal exposure to xylene and ethylbenzene in air were collected using diffusive samplers. Urine samples of the spray painters were collected after a month-long holiday leave and during the pre- and post-workshifts. Urine samples of sandblasting workers and office staffs were gathered after their shift. Urinary mandelic acid and methyl hippuric acid were used as biological indices of dose of ethylbenzene and xylene, respectively. Urinary 8-OHdG was used as biomarker of oxidative DNA damage. The post-workshift concentration of urinary 8-OHdG for 10 spray painters (30.3 ± 9.28 μg g(-1) creatinine) significantly exceeded that of holiday leave (7.20 ± 1.08 μg g(-1) creatinine; P = 0.001). The post-workshift concentration of urinary 8-OHdG was higher among 15 spray painters (29.0 ± 6.52 μg g(-1) creatinine) than sandblasting workers (9.14 ± 2.05 μg g(-1) creatinine; P = 0.01) and office staffs (8.35 ± 0.84 μg g(-1) creatinine; P = 0.007). A stepwise regression model revealed an 8.11 μg g(-1) creatinine increase per 1 p.p.m. increase in ethylbenzene [95% confidence interval (CI) 4.13-12.1]. A stepwise regression model revealed an increase of 6.04 μg g(-1) creatinine (95% CI 2.23-9.84) per 1 p.p.m. in ethylbenzene after adjustment of age (95% CI 2.23-9.84). This pilot study suggests that occupational exposure to paint increases oxidative DNA injury. Moreover, urinary 8-OHdG levels displayed greater DNA damage in spray painters compared to other unexposed groups and their holiday leave samples. A significant correlation was found between urinary 8-OHdG and the exposure to ethylbenzene. The ethylbenzene exposure could not explain all urinary 8-OHdG measured. Other components of paint deserve further investigation.     

Oxidative DNA damage estimated by plasma 8-hydroxydeoxyguanosine (8-OHdG): influence of 4, 4'-methylenebis (2-chloroaniline) exposure and smoking

Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4'-methylenebis (2-chloroaniline) (MBOCA)-exposed workers. By measuring the plasma level of 8-hydroxydeoxyguanosine (8-OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8-OHdG. We undertook a cross-sectional survey at four MBOCA-producing factories in Taiwan (158 subjects). Plasma 8-OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (>20 microg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA-exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8-OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8-OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8-OHdG levels than non-smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8-OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.     

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.     

8-羟基脱氧鸟嘌呤作为可溶性铬盐职业接触者生物标志物的研究

[目的]了解职业接触可溶性铬盐人群尿中8-羟基脱氧鸟嘌呤(8- OHdG)含量及其影响因素,探讨其作为职业接触人群生物标志物的可行性.[方法]2006年,选择济南市某铬盐生产企业114名重铬酸钾作业的健康劳动者作为接触组,以无毒物接触史的当地健康农民30名为对照组,测定2组人群尿液中8-OHdG水平与作业环境铬盐浓度,测定接触组外周血淋巴细胞DNA链断裂水平、红细胞与尿液中铬浓度.[结果]尿液中8-OHdG水平接触组为(1 240.494±1 603.918) μg/L,对照组为(468.871±908.460) μg/L(P<0.01);尿液中8-OHdG水平与空气中个体铬盐暴露水平、红细胞中铬浓度水平、外周血淋巴细胞DNA链断裂水平的相关系数(r)分别为0.333、0.230、0.396(P<0.01);多元线性回归分析显示,铬盐劳动者年龄、接触铬盐的年限、空气中铬盐浓度对尿液中8-OHdG水平影响显著.[结论]尿液中8-OHdG水平可以作为职业接触可溶性铬盐劳动者遗传损伤效应性生物标志物,可望用于职业接触可溶性铬盐劳动者生物监测及健康危险性的评价.     

Occupational exposure to asphalt fume can cause oxidative DNA damage among road paving workers

Objectives

We designed the present study to determine the effect of occupational exposure to asphalt fumes on oxidative status and DNA damage in road paving workers.

Methods

Sixty road paving workers exposed to asphalt fumes and forty non‐exposed control subjects were recruited. Occupational exposure to PAHs was assessed by urinary 1‐hydroxypyrene (1‐OHP) excretion. Serum thiol disulfide homeostasis (TDH), total oxidant status (TOS) and total antioxidant status (TAS) and urinary 8‐hydro‐deoxyguanosine (8‐OH‐dG) level were evaluated by automated colourimetric method.

Results

The urinary concentrations of 1‐OHP and 8‐OH‐dG were significantly higher in the exposed group than in the control group (P < 0.001). Disulfide/thiol ratio, TOS, and TAS were also significantly higher for the asphalt workers. A positive correlation existed between urinary 1‐OHP and 8‐OH‐dG, TOS and TAS.

Conclusion

Study results indicate that exposure to PAHs induces oxidative stress and causes genotoxic effects in asphalt workers.

     

Dose-dependent production of urinary naphthols among workers exposed to jet fuel (JP-8)

BACKGROUND: Jet propulsion fuel-8 (JP-8) is one of the largest sources of chemical exposures among Air Force personnel. Urinary naphthols have been suggested as useful biomarkers of exposure to JP-8. METHODS: Multivariate linear regression models were applied to evaluate the effects of environmental and work-related factors upon production of urinary naphthols among 323 Air Force personnel. RESULTS: Naphthalene exposure, smoking status, and their interaction, plus self-reported skin irritation explained about two-thirds of the variation in naphthol levels. The exposure-smoking interaction was consistent with induction by smoking of one or more steps in the metabolism of naphthalene and naphthalene-1,2-oxide (NapO). A supralinear dose-response relationship was observed between urinary naphthols and naphthalene exposure. CONCLUSIONS: Urinary naphthols were associated with specific sources of exposure to JP-8, arising from both inhalation and dermal contact. Smokers and nonsmokers metabolized naphthalene at different rates, consistent with induction of at least two metabolic pathways by smoking.     

Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells

8-Hydroxydeoxyguanosine (8-OH-dG) is a typical form of oxidative DNA damage, which causes mutations in vitro and in vivo. To develop a simple method of testing the carcinogenicity of fibrous materials, the formation of 8-OH-dG was determined in the DNA of J774 cells, an established reticulum cell sarcoma line, after treatment with various natural and man-made mineral fibers. The amount of 8-OH-dG was determined using high-pressure liquid chromatography (HPLC) equipped with an electrochemical detector (ECD). We tested three natural mineral fibers (crocidolite, amosite, and chrysotile) and three man-made mineral fibers (ceramic, glass, and potassium octatitanate). Among them, a significant increase in 8-OH-dG formation was observed in the crocidolite- and amosite-treated cells. We also measured the amount of tumor necrosis factor (TNF) produced by J774 cells incubated with the fibrous materials. Cellular TNF production increased after treatment with all the fibers tested, but it was not statistically significant except in the case of chrysotile. Therefore, these results indicate that the mechanism of TNF production is different from that of 8-OH-dG formation, and that the carcinogenicity of various fibrous materials can be better evaluated by measuring the 8-OH-dG level in J774 cellular DNA after treatment with these fibers. Received: 1 October 1996 / Accepted: 28 March 1997     

Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates

Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter 相似文献   

Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E

Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.     

The stability of the oxidative stress marker, urinary 8-hydroxy-2'- deoxyguanosine (8-OHdG), when stored at room temperature

We examined the stabilities of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) stored at room temperature (25 degrees C) for 24 h or at -80 degrees C for 800 days. Subjects were 19 males and 17 females aged 23-58 yr for the 24-h study, and 9 males and 4 females aged 24-54 yr for the 800-day study. We obtained information on the subjects by questionnaires and interviews. The level of urinary 8-OHdG was measured by HPLC using two-step separations. There were no significant changes of amount of urinary 8-OHdG under either storage conditions. We conclude that urine samples can be stored at 25 degrees C and below for 24 h, when the research purpose includes the determination of urinary 8-OHdG. Urinary 8-OHdG was also stable for over two years when stored at -80 degrees C.     

铬化合物对人体外淋巴细胞DNA损伤研究

目的　研究铬化合物对人体外淋巴细胞 DNA损伤。　方法　应用新型彗星图象分析系统以及单细胞凝胶电泳 (SCGE) ,检测六价铬对外周血处理 1h后 DNA的损伤程度。　结果　作者开发的彗星图象分析系统能较好地应用于单细胞凝胶电泳 ,剂量大于 6 0μmol/L的重铬酸钾均可引起 DNA损伤 ,并且存在明显的剂量反应关系。　结论　六价铬可以诱发体外淋巴细胞 DNA损伤     

Association between plasma BPDE-Alb adduct concentrations and DNA damage of peripheral blood lymphocytes among coke oven workers

Objectives

Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons (PAHs) can induce both benzo[a]pyrene‐r‐7, t‐8, t‐9,c‐10‐tetrahydotetrol‐albumin (BPDE‐Alb) adducts and DNA damage. However, the relation between these biomarkers for early biological effects is not well documented in coke oven workers.

Methods

In this study, the authors recruited 207 male workers exposed to COE and 102 controls not exposed to COE in the same steel plant in northern China. They measured BPDE‐Alb adduct concentrations in plasma with reverse‐phase high performance liquid chromatography and DNA damage in peripheral blood lymphocytes with alkaline comet assay.

Results

The results showed that the median concentration of BPDE‐Alb adducts in the exposed group (34.36 fmol/mg albumin) was significantly higher than that in the control group (21.90 fmol/mg albumin, p = 0.012). The mean Olive tail moment (Olive TM) of DNA damage in the exposed and control groups were 1.20 and 0.63, respectively (p = 0.000). Multivariate logistic regression analysis revealed that the odds ratio (OR) for BPDE‐Alb adduct and Olive TM associated with the exposure were 1.72 (95% CI 1.06 to 2.81) and 1.96 (95% CI 1.20 to 3.19), respectively. These results show significant correlations between the concentrations of BPDE‐Alb adduct and Olive TM levels in exposed group (r = 0.235, p = 0.001) but not in control group (r = 0.093, p = 0.353).

Conclusion

The results suggest that occupational exposure to COE may induce both BPDE–Alb adducts and DNA damage in the lymphocytes of coke oven workers and that these two markers are useful for monitoring exposure to COE in the workplace.Coke oven workers are exposed to coke oven emissions (COE) that contain a wide variety of volatile organic solvents and particulates, especially polycyclic aromatic hydrocarbons (PAHs).¹ Epidemiological studies suggest an aetiological link between carcinogenic PAHs exposure and lung cancer risk in coke oven workers exposed to COE, and coke oven workers were found to have a three‐ to sevenfold increased risk for developing lung cancer.^1,2Benzo[a]pyrene (B[a]P), the most potent and well‐studied carcinogen in PAHs mixtures, has been used as an indicator for carcinogenic PAHs.^3,4 The metabolic activation of B[a]P by cytochromes P450 produces 7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene (BPDE), the ultimate carcinogenic form that can bind covalently to DNA and proteins.⁵ Therefore, both DNA and protein adducts are thought to be biologically effective dose biomarkers of PAHs.⁶ There are a number of published reports on DNA adducts in workers exposed to PAHs.^7,8 Although DNA adducts determined using DNA from white blood cells may not reflect the levels of DNA damage in the target tissues,⁹ DNA from the target tissues is usually not readily accessible in human biomonitoring. The albumin adducts in blood are considered a surrogate biomarker of the effective dose of exposure and are not considered to be directly involved in carcinogenesis,¹⁰ because they represent only one month exposure within the half‐life of the albumin.¹¹The carcinogenicity induced by PAHs compounds is believed to be initiated by DNA damage.¹² A wide variety of non‐bulky base damage and single‐strand breaks are formed during metabolic activation of PAHs and involved in PAHs carcinogenesis,^13,14 and these types of DNA damage can be detected by comet assay and used as a marker of early biological effects of DNA‐damaging agents in the living environments and occupational workplaces.^15,16,17 Specifically, the alkaline comet assay (pH>13) can detect DNA strand breaks, alkali‐labile sites, and incomplete excision repair sites.¹⁸ However, the published results of the relation between COE exposure and DNA damage in the lymphocytes measured by comet assay are not consistent.^{19,20,21,22,23} For example, some investigations have shown that there was a significant increase in DNA damage in workers exposed to COE compared with unexposed controls.^19,20,22 However, others^21,23 did not find any effect of occupational exposure on the levels of DNA damage measured with the comet assay, possibly due to small sample sizes in these studies.In the exposure‐to‐disease pathogenic pathway, biomarkers that can provide information of exposure to carcinogenic agents (biomarkers of exposure) and early changes caused by the agents (biomarkers of effect) are needed in epidemiological studies of cancer risk. However, the levels of exposure biomarkers and their associations with early biological effects in coke oven workers are not well documented. Some authors have reported significant association between biomarkers of internal dose (1‐hydroxypyrene) and effect biomarkers (comet assay, sister chromatid exchanges, micronuclei, chromosomal aberrations, and 8‐oxo‐7, 8‐dihydro‐2''‐deoxyguanosine) for coke oven workers exposed to PAHs,^20,22,23 but these were not confirmed by other studies.^21,26 One reason for this inconsistency is the levels of 1‐hydroxypyrene revealing recent exposure to COE or different sample size (from 83 to 217 subjects included). A positive association between biologically effective‐dose biomarkers (aromatic‐DNA adducts) with effect biomarkers (8‐oxo‐7, 8‐dihydro‐2''‐deoxyguanosine) among 149 coke oven workers was previously reported.²⁶ To our knowledge, there was no reported investigation on the correlation between BPDE‐Alb adduct concentrations and DNA damage in lymphocytes in coke oven workers, although these two biomarkers were individually applied in some occupational biomonitoring. Therefore, we further assessed whether occupational exposure to COE resulted in high concentrations of BPDE–Alb adducts and DNA damage and their possible correlation in 207 male workers exposed to COE and 102 male unexposed controls.     

Urinary excretion of an oxidative stress marker, 8-hydroxyguanine (8-OH-Gua), among nickel-cadmium battery workers

The relationship between oxidative stress and carcinogenic metals including nickel and cadmium is a matter of interest. To assess the oxidative stress status of workers exposed to nickel and cadmium simultaneously, we determined urinary excretion of 8-hydroxyguanine (8-OH-Gua), a urinary oxidative stress marker. Our subjects were 66 (64 males and 2 females) nickel-cadmium battery workers. Spot urine and blood samples were collected. The levels of cadmium in blood (Cd-B) and nickel in urine (Ni-U) were determined by graphite furnace atomic absorption spectrophotometry. 8-OH-Gua in urine was analyzed using a high performance liquid chromatography-electrochemical detector (HPLC-ECD) system. Data on age, sex, duration of present work and smoking status were also obtained from each subject. Creatinine-adjusted 8-OH-Gua was significantly correlated with age, Ni-U and Cd-B in univariate analysis, while multivariate analysis revealed that Ni-U and Cd-B were significant independent variables and that these two biological exposure indices were positively correlated with 8-OH-Gua. The data were also analyzed in the context of mixture toxicity. The subjects were divided into groups based on median level of Ni-U and Cd-B (2.86 mug/g creatinine and 0.23 mug/dl, respectively). Workers with high Ni-U/high Cd-B (Group IV) had the highest levels of 8-OH-Gua levels (GM (GSD), 21.7(2.0)), followed by those with high Ni-U/low Cd-B (11.5(1.6) Group III), those with low Ni-U/high Cd-B (8.9(1.9) Group II), and those with low Ni-U/low Cd-B (8.5(1.5) Group I). The p values of Students' t-tests between Group I and Group II, III and IV were 0.847, 0.050 and <0.001, respectively. The combined effect of Cd and Ni on the urinary excretion of 8-OH-Gua departed from additivity.     

Rapid and intermediate N-acetylators are less susceptible to oxidative damage among 4,4′-methylenebis(2-chloroaniline) (MBOCA)-exposed workers

Objectives

In this study, we explored the association between a marker of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG), and genetic polymorphism of the carcinogen-metabolizing enzyme N-acetyltransferase 2 (NAT2) among 4,4′-methylenebis(2-chloroaniline) (MBOCA)-exposed workers.

Methods

The study population was recruited from four MBOCA-producing factories, and included 57 MBOCA-exposed workers and 101 unexposed control workers. Personal characteristics were collected by questionnaire. Plasma 8-OHdG levels were measured by LC/MS/MS. NAT2 alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP).

Results

NAT2 polymorphism influenced the plasma 8-OHdG levels of MBOCA-exposed workers, but not of non-exposed workers. No difference between exposed and control groups was found for the crude 8-OHdG levels among rapid, intermediate, and slow acetylators. After adjusting for gender, age, smoking, and alcohol consumption habit, the 8-OHdG concentration in the MBOCA-exposed workers was 0.18 pg/ml (95% CI −1.80 to −0.12) lower than the control group among rapid and intermediate acetylators. However, the difference between exposed and control groups was not significant for slow acetylators.

Conclusion

Gene–environment interactions could play a role in the carcinogenesis of occupational MBOCA exposure. We suggest that the impact of the NAT2 acetylator status is low, if at all, on the generation of the oxidative stress marker 8-OHdG in the investigated exposed group.     

Lower serum levels of beta-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine. The LiVicordia study

OBJECTIVE: In 1995, middle-aged Lithuanian men had a four-fold higher risk than Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia study had reported significantly lower levels of the lipid-soluble antioxidants lycopene, beta-carotene, and gamma-tocopherol among Lithuanian men than among Swedish men. We examined whether there were differences in urinary 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups of men. METHODS: Using automated coupled column high-performance liquid chromatography with electrochemical detection, we examined 50-y-old men randomly sampled from Link?ping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with regard to urinary concentrations of 8-OHdG. RESULTS: Levels of 8-OHdG were higher in the Lithuanian men than in the Swedish men (20.9 +/- 0.91 versus 14.9 +/- 0.75 nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non-smokers (P < 0.001). Serum levels of alpha- and beta-carotene were inversely correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking and low levels of beta-carotene contributed significantly to higher oxidative DNA damage expressed as urinary 8-OHdG. CONCLUSIONS: These findings indicate that increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in Lithuanian men. They supported previous suggestions that increased oxidative stress may be one factor behind the higher mortality in Lithuanian men.     

Blood lead level to induce significant increase in urinary delta-aminolevulinic acid level among lead-exposed workers: a statistical approach

The present study was initiated to examine the quantitative relationship between blood lead (Pb-B) and urinary delta-aminolevulinic acid (ALA-U) among Pb-exposed workers, and to find a threshold Pb-B level to induce an increase in ALA-U. For this purpose, pairs of venous blood and spot urine samples were collected from 8,274 men and 5,856 women (14,130 workers in total) who were occupationally exposed to inorganic lead. The blood and urine samples were analyzed for Pb-B and ALA-U by atomic absorption spectrometry and colorimetry, respectively, and the correlation between pairs of measures were subjected to statistical analysis. The assumption of the 3rd degree regression for correlation gave a substantially greater correlation coefficient (0.645 for men and 0.619 for women) than 1st or 2nd degree regression, whereas only very small improvement in the coefficient was achieved with 4th to 6th degree ones. Logarithmic conversion of the parameters was not effective in improving the correlation. The assumption of the 3rd degree regression followed by calculation of the local minimum gave 22, 29 and 23 micrograms/100 ml Pb-B for men, women, and men + women, respectively, as the threshold Pb-B to induce ALA-U increase. Pb-B to elevate ALA-U to the 95% upper normal limit (8 mg/l, common to men and women) was 62, 50 and 58 micrograms/100 ml for men, women and men + women, respectively. The validity of the 3rd degree regression assumption as a tool to calculate a threshold from experimental or epidemiological data is discussed.     

Analysis of 8-hydroxyguanine (8-OH-Gua) released from DNA by the formamidopyrimidine DNA glycosylase (Fpg) protein: a reliable method to estimate cellular oxidative stress

To improve the analyses of a form of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), we treated isolated DNA with formamidopyrimidine DNA glycosylase (Fpg) and analyzed the released 8-OH-Gua by using a high-performance liquid chromatography system equipped with an electrochemical detector (HPLC-ECD). The human lung carcinoma cells (A549) and human keratinocyte (HaCaT) were irradiated with gamma-rays. After the isolated DNA was treated with the Fpg protein, we analyzed the released 8-OH-Gua by using an HPLC-ECD. With this method, the background level of 8-OH-Gua in DNA from human lung carcinoma cells was determined to be 3.4 residues per 10(7) guanine (Gua). A similar background level of 8-OH-Gua (3.1 residues per 10(7) Gua) was also detected in human keratinocyte DNA with this method. These background 8-OH-Gua levels in cellular DNA are comparable to that obtained previously by an analysis of 8-OH-dGMP after nuclease P1 digestion of cellular DNA (4.3 residues per 10(7) dCMP). A dose-dependent increase of 8-OH-Gua (0.17/10(7) Gua/Gy) was observed after cells were irradiated with gamma-rays. Twenty hours after gamma-irradiation with 60 Gy, 75% of the 8-OH-Gua produced in keratinocyte DNA was repaired. With our new analysis method, it is possible to detect the small changes in the 8-OH-Gua levels in cellular DNA induced by various environmental factors.     

Smoking modify the effects of polycyclic aromatic hydrocarbons exposure on oxidative damage to DNA in coke oven workers

Purpose

Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage.

Methods

The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography.

Results

The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P?<?0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P?<?0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32–13.86 and OR 5.05, 95% CI 1.63–15.67, respectively).

Conclusions

Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.