Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/- control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.     

Aldh2 knockout mice were more sensitive to DNA damage in leukocytes due to ethyl tertiary butyl ether exposure

To clarify the genotoxicity of ethyl tertiary butyl ether (ETBE), a gasoline additive, male and female C57BL/6 mice of Aldh2+/+ and Aldh2-/- genotypes, aged 8 wk, were exposed to 0, 500, 1,750, or 5,000 ppm ETBE for 6 h/day, 5 d per week for 13 wk. DNA damage in leukocytes was measured by the alkaline comet assay and expressed quantitatively as Tail Intensity (TI). For male mice, TI was significantly higher in all three groups exposed to ETBE than in those without exposure within Aldh2-/- mice, whereas within Aldh2+/+ mice, TI increased only in those exposed to 5,000 ppm of ETBE as compared with mice without exposure. For female mice, a significant increase in TI values was observed in the group exposed to 5,000 ppm of ETBE as compared with those without exposure within Aldh2-/- mice; TI in Aldh2-/- mice exposed to 1,750 and 5,000 ppm was significantly higher than in Aldh2+/+ mice without exposure. TI did not significantly increase in any of the groups exposed to ETBE within female Aldh2+/+ mice. Based on the results we suggest that Aldh2-/- mice are more sensitive to DNA damage caused by ETBE than Aldh2+/+ mice and that males seem more susceptible to this effect than females.     

Lack of aldehyde dehydrogenase ameliorates oxidative stress induced by single-dose ethanol administration in mouse liver.

Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is far more common in East Asian countries. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people who have ALDH2*2, as the mutated ALDH2 lacks acetaldehyde metabolizing activity. On the other hand, it is well established that metabolism of ethanol causes oxidative stress in liver tissue. To examine the consequences of this polymorphism on ethanol-induced oxidative stress in liver tissue, we conducted a study using Aldh2 knockout mice. Aldh2+/+ and Aldh2-/- mice were orally administered ethanol at a dose of 5g/kg body weight. Levels of malondialdehyde, an indicator of oxidative stress, and glutathione, a key antioxidant, in liver tissue were analyzed 0-24h after administration. Levels of malondialdehyde were significantly lower in Aldh2-/- mice than in Aldh2+/+ mice at 12h after injection, while levels of glutathione were higher in Aldh2-/- mice than in Aldh2+/+ mice at 6 and 12h after injection. Our results suggest that a lack of ALDH ameliorates ethanol-induced oxidative stress in liver tissue.     

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.     

Increased levels of 8-hydroxy-2 -deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren

Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean +/- SE, 16.0 +/- 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children.     

Chromium (VI) induced oxidative damage to DNA: increase of urinary 8-hydroxydeoxyguanosine concentrations (8-OHdG) among electroplating workers

Aims: To investigate the concentration of urinary 8-hydroxydeoxyguanosine (8-OHdG) among electroplating workers in Taiwan.

Methods: Fifty workers were selected from five chromium (Cr) electroplating plants in central Taiwan. The 20 control subjects were office workers with no previous exposure to Cr. Urinary 8-OHdG concentrations were determined using high performance liquid chromatography with electrochemical detection.

Results: Urinary 8-OHdG concentrations among Cr workers (1149.5 pmol/kg/day) were higher than those in the control group (730.2 pmol/kg/day). There was a positive correlation between urinary 8-OHdG concentrations and urinary Cr concentration (r = 0.447, p < 0.01), and urinary 8-OHdG correlated positively with airborne Cr concentration (r = 0.285). Using multiple regression analysis, the factors that affected urinary 8-OHdG concentrations were alcohol, the common cold, and high urinary Cr concentration. There was a high correlation of urinary 8-OHdG with both smoking and drinking, but multiple regression analysis showed that smoking was not a significant factor. Age and gender were also non-significant factors.

Conclusion: 8-OHdG, which is an indicator of oxidative DNA damage, was a sensitive biomarker for Cr exposure.

     

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.     

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   

焦炉工人血清谷胱甘肽硫转移酶活力和尿8-羟基脱氧鸟苷水平

目的 探讨血清谷胱甘肽硫转移酶（GST）和尿8-羟基脱氧鸟苷（8-OHdG）作为焦炉工人多环芳烃（PAHs）暴露生物监测标志的可行性.方法 用高效液相色谱-电化学方法和试剂盒分别检测47名男性焦炉工和31名男性对照者尿8-OHdG水平和血清GST活力;尿1-羟基芘（1-OHP）作为PAHs接触的内暴露标志,采用碱水解-高效液相色谱方法分析.结果 焦炉工人尿1-OHP浓度的中位数（P25～P75）为[5.7（1.4～12.0）μmol/mol Cr],血清GST活力为[22.1（14.9～31.2）U/ml],尿8-O-HdG水平为[1.9（1.4～15.4）μmol/mol Cr],均高于对照组工人[3.0（0.5～6.4）μmol/mol Cr、13.1（9.5～16.7）U/ml、1.3（1.0～4.0）μmol/mol Cr],差异均有统计学意义（P＜0.05或P＜0.01）.以吸烟分层,两组工人尿1-OHP浓度和血清GST活力仅在吸烟者中、尿8-OHdG水平仅在非吸烟者中差异有统计学意义（均P＜0.01）.焦炉工人血清GST活力和尿1-OHP浓度呈正相关（rs=0.31,P＜0.01,n=78）.多元Logistic回归分析显示,与对照工人相比,焦炉工人血清GST活力＞16.7 U/ml和尿8-OHdG水平＞1.8 μmol/mol Cr的OR值分别为13.2和4.4;高体重指数是影响尿8-OHdG水平下降的独立因素.结论 焦炉工人血清GST活力增强和氧化性DNA损伤增加,吸烟和职业暴露有交互作用;血清GST有可能作为PAHs暴露评价的生物标志;尿8-OHdG检测有助于焦炉工肺癌危险度评价.     

8-Hydroxydeoxyguanosine in human leukocyte DNA and daily health practice factors: effects of individual alcohol sensitivity.

A typical oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), was evaluated in human polymorphonuclear leukocytes (PMN) and mononuclear leukocytes (MN) by an anaerobic determination method. The mean 8-OHdG values were the lowest level ever reported [PMN, 3.07 +/- 1.45; MN, 2.37 +/- 1.21 8-OHdG/10(6) deoxyguanosine molecules (dG); n = 92]. According to a self-administered questionnaire to 92 healthy male workers, the relationship was investigated between 8-OHdG in leukocytes and daily health practice factors, that is, the frequency of physical exercise, smoking status, alcohol drinking, nutritional balance, and the degree of mental stress. A significant difference was observed only in alcohol drinking in subjects classified by aldehyde-dehydrogenase 2 isozyme (ALDH2) genotype. Habitual alcohol intake appeared to increase 8-OHdG in PMN from ALDH2-deficient subjects. Neither age, body mass index, nor any other factors examined showed any significant correlation with the 8-OHdG levels in leukocytes.     

吸烟和年龄对电子垃圾拆解工人尿液中8-羟基脱氧鸟苷的影响

目的 研究吸烟和年龄对电子垃圾拆解工人尿液中8-羟基脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)的影响.方法 采用固相萃取-高效液相色谱电化学检测器(SPE-HPLC-ECD)方法,检测64名电子垃圾拆解男性工人上班前和下班后尿液中8-OHdG浓度.按照吸烟情况和工人的年龄分别对数据进行统计分析.结果 相对于吸烟者(42名),不吸烟者(22名)尿中8-OHdG浓度明显的增高,上班前,不吸烟组的工人尿液中的8-OHdG浓度为(8.25±4.23)μmol/mol肌酐,吸烟组工人尿液中8-OHdG浓度为(5.44±1.18)μmol/mol肌酐,两者差异无统计学意义(t=-0.81,P=0.42).而在下班后,不吸烟组的工人尿液中的8-OHdG浓度为(43.12±16.19)μmol/mol肌酐,大约是吸烟组工人尿液中8-OHdG浓度[(14.82±2.51)μmol/mol肌酐]的3倍.经过1 d暴露下班后,吸烟和不吸烟工人尿液中的8-OHdG浓度差异具有统计学意义(t=-2.33,P<0.05).按照工人的年龄分组,上班前,19岁～(6名)、20岁～(22名)、30岁～(23名)、40～49岁(11名)组工人尿中8-OHdG浓度分别为(1.86±0.66)、(3.57±0.54)、(8.12±4.10)、(11.39±3.70)μmol/mol肌酐,组间差异没有统计学意义(F=0.98,P=0.41);但经过1 d的暴露,下班后,19岁～、20岁～、30岁～、40～49岁组工人尿中8-OHdG浓度分别为(4.19±2.85)、(19.89±5.26)、(28.89±14.61)、(34.94±12.50)μmol/mol肌酐,组间差异具有统计学意义(F=4.81,P=0.03).结论 吸烟对拆解工人尿中8-OHdG浓度有一定的抑制作用,尿中8-OHdG浓度随年龄增高而增加.     

Metallothionein in mice reduces intestinal zinc loss during acute endotoxin inflammation, but not during starvation or dietary zinc restriction

Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine the influence of MT on Zn retention and the metabolic consequences of 2 d food deprivation, with and without inflammation induced by intraperitoneal injection of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn concentration in MT+/+ mice from 5.9 +/- 0.2 micromol/g on d 1 to 2.2 +/- 0.2 micromol/g on d 2, but not in MT-/- mice, 5.9 +/- 0.2 and 5.7 +/- 0. 5 micromol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d did not lower fecal Zn concentration in either genotype, although in MT+/+ mice, urinary Zn excretion was reduced from 12.7 +/- 1.3 nmol on d 1 to 5.9 +/- 1.8 nmol on d 2 and plasma Zn concentration was lowered to 9.8 +/- 0.4 micromol/L. Zn was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8 +/- 2.0 nmol on d 1, 9.3 +/- 2.9 nmol on d 2 and 13.0 +/- 1.0 micromol/L. LPS injection resulted in much higher total liver Zn (677 +/- 27 nmol) and MT (106 +/- 2 nmol Cd bound/g) than starvation (Zn = 405 +/- 21, MT = 9 +/- 3) in MT+/+ mice after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed. When uninduced, typically during Zn deficiency, MT appears to conserve Zn and body mass by reducing only urinary and other nonintestinal Zn losses.     

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 urinary 8-hydroxy-2'-deoxyguanosine and arsenic in glass production workers

A total of 130 male glass workers, including 33 administrative workers, 18 batch house workers, 42 craftsmen, and 37 melting process workers, were recruited to investigate the potential DNA damage resulting from toxic element exposure. The occupational exposure to trace elements, including arsenic (As), cadmium (Cd), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se), was estimated by their urinary levels as internal doses. In addition, all participants filled a self-filled questionnaire indicating their individual information. The average levels of urinary As, Cd, Mn, Ni, Pb, Se, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were 282.3 ± 464.6, 3.07 ± 5.39, 3.81 ± 11.43, 81.48 ± 138.9, 18.23 ± 49.61, 165.2 ± 224.9, and 17.21 ± 26.34 μg/g creatinine, respectively. The urinary levels of 8-OHdG and toxic elements were strongly associated with the work nature of the worker, with an exception of Mn and Pb. In contrast, the levels of toxic element were not influenced by age, smoking behavior, and alcohol consumption. The urinary 8-OHdG was found significantly higher in higher internal exposure groups of As, Cd, Ni, and Se. However, the stepwise multiple regression models showed that urinary 8-OHdG was only associated with urinary As and heat stress but inversely with age.     

8-Hydroxydeoxyguanosine in leukocyte DNA and urine of quartz-exposed workers and patients with silicosis

Objective: To examine radical-induced DNA damage and its elimination in workers exposed to quartz and in patients with silicosis, and to assess the relationship of these effects to lung function. Methods: Blood and spontaneous urine samples were obtained from active, quartz-exposed workers without silicosis (n=63), and from retired workers with silicosis (n=42). Levels of 8-hydroxydeoxyguanosine (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use of high-performance liquid chromatography coupled with ultra violet- (UV) and electrochemical detection. Results: No significant differences in the mean levels of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between silicosis patients and quartz-exposed healthy workers. However, in the group of silicosis patients with increased oxidative DNA damage the urinary excretion of 8-OHdG was lower than in the corresponding group of active workers without silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8-OHdG in DNA correlated negatively, with forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC). Healthy workers with a personally estimated high dust exposure in the workplace showed higher levels of 8-OHdG in DNA than did workers with moderate dust exposure. No association of 8-OHdG formation and/or elimination with duration of employment, field of activity, smoking or age was found. Conclusion: Our findings suggest that a less effective repair of 8-OHdG is associated with a higher degree of pulmonary airway obstruction in patients with silicosis. Received: 13 August 1999 / Accepted: 5 January 2000     

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.     

Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. There is increasing health concerns regarding low-level exposure to BPA among the general population. The aim of this study was to determine the association between BPA exposure with oxidative stress and inflammation in adult populations. A cross-sectional study was conducted. This study included 485 adults (259 men, 92 premenopausal women, and 134 postmenopausal women) living in general communities within large cities. Urinary concentrations of BPA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), white blood cell (WBC) count, and C-reactive protein (CRP) were measured. Multivariate analyses were applied to determine the associations of BPA exposure with oxidative stress and inflammation. The geometric means of urinary BPA for men, premenopausal women, and postmenopausal women were 0.53, 0.61, and 0.58 μg/g cr, respectively. The urinary BPA concentrations were positively associated with MDA, 8-OHdG, and CRP levels in the postmenopausal women; however, such associations did not exist in men and premenopausal women. The findings of this study suggest that BPA exposure would promote oxidative stress and inflammation, in which postmenopausal women are likely to be more susceptible to BPA-induced health effects.     

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.     

Acetaldehyde-reinforcing effects: differences in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

It has been suggested that acetaldehyde has a biphasic effect on voluntary alcohol consumption. At low brain concentration, it might exert reinforcing effects, whereas high acetaldehyde levels would be predominantly aversive. The objective of the current study was to compare the effect of an intraperitoneal dose of acetaldehyde (50 mg/kg) in high-alcohol-drinking (UChB) and low-alcohol-drinking (UChA) rat lines, which differ in the activity of the brain mitochondrial class 2 aldehyde dehydrogenase (ALDH2) as a consequence of differences in their ALDH2 genotypes. A classical place-conditioning procedure was used to determine the reinforcing or aversive (or both) effects of acetaldehyde in ethanol-naive UChB and UChA rats. Environmental cues were paired with an intraperitoneal 50-mg/kg injection of acetaldehyde. On 10 consecutive days, each rat received one place conditioning per day; the acetaldehyde-pairing was alternated with saline-pairing. Results showed that conditioning with the 50-mg/kg dose of acetaldehyde induced place preference in UChB rats and place aversion in UChA rats. In a second experiment, UChB and UChA rats, pretested for ethanol preference, were injected with one 50-mg/kg dose of acetaldehyde or saline and tested for their voluntary ethanol consumption during 4 weeks. Results showed that the acetaldehyde dose induced a persistent and long-lasting enhancement of ethanol intake in UChB rats, but not in UChA rats. These results, together with the finding that after administration of a 50-mg/kg dose of acetaldehyde cerebral venous blood acetaldehyde levels in UChA rats were consistently higher than levels in UChB rats, support the suggestion that differential acetaldehyde levels, differential brain ALDH2 activity, or both were responsible for the different effects of acetaldehyde in the two rat lines.