Determinants of benzo[a]pyrene diol epoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons

The present study was undertaken among 260 subjects [133 controls and 127 persons exposed to polycyclic aromatic hydrocarbons (PAHs)] from two steel foundries and a graphite electrode producing plant in order to investigate the relationship between the benzo[a]-pyrene-diol epoxide adducts to albumin (BPDE-alb) and the intensity of exposure to PAHs. Blood samples were collected from each subject and BPDE-alb adduct determination was performed using a high-pressure liquid chromatography technique with fluorescence detection. Exposure to PAHs was assessed by measuring airborne concentration of 13 PAHs including benzo[a]pyrene (BaP) using personal air sampling and 1-hydroxypyrene excretion (1-HOP) in postshift urine. Significantly higher BPDE-alb adduct levels were observed in exposed workers compared to controls but wide interindividual variation was observed between subjects with the same level of exposure. BPDE-alb adduct level was weakly but significantly associated with the airborne concentrations of total PAHs (r = 0.35, P = 0.0001) and BaP (r = 0.30, P = 0.0001), and urinary 1-HOP excretion (r = 0.29, P = 0.0001). Alcohol and dietary habits, place of residence, and renal and hepatic status were not found to influence the concentration of BPDE-alb adducts significantly. However, for the same level of exposure to BaP, smokers had a higher probability of having an elevated BPDE-alb adduct level than nonsmokers. As long as BPDE-protein adduct levels have not been demonstrated to be better related to the risk of adverse genotoxic effects caused by PAHs in target organs than the 1-HOP level in urine, the latter remains the most practical biological parameter for assessing the risk of exposure to PAHs.     

The effect of relevant genotypes on PAH exposure-related biomarkers

Polycyclic aromatic hydrocarbons (PAHs) in coke oven emissions cause a cancer risk to humans. In a comprehensive biomonitoring study among Estonian coke oven workers, we looked at the effect of genetic polymorphisms in metabolic enzymes on urinary mutagenicity, 1-hydroxypyrene (1-OHP) concentration in urine, and aromatic DNA adducts in white blood cells (WBCs). Coke oven workers were sampled twice (samplings I and II), and controls only once at the time of sampling I. Urinary mutagenicity was measured using the Ames test. CYP1A1, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) genotypes were analyzed by polymerase chain reaction (PCR). Urinary mutagenicity did not differ between exposed and controls, but those coke oven workers who were smokers had significantly higher (P=0.0002) mutagenic activity in urine than nonsmokers. Urinary mutagenicity was moderately correlated to levels of 1-OHP and aromatic DNA adducts, the P values ranging from 0.0005 to 0.002. Carriers of a variant allele in exon 4 of mEH (Arg139) had elevated urinary mutagenicity (sampling I). In addition, urine mutagenicity of persons with predicted high mEH activity was significantly higher. Smoking habit did not explain the differences observed in urinary mutagenicity between mEH phenotype or genotype subgroups. Variation in exon 3 of mEH (His113) was related to a significantly (P=0.01) higher 1-OHP concentration in exposed workers (sampling II). Workers from sampling I who had an Arg139 variation in mEH had lower levels of adducts in lymphocytes (P=0.01) than others, while airborne benzo[a]pyrene (B[a]P) and His113 variation affected interactively on adduct levels. Our study shows that a comprehensive assessment of exposure is essential for elucidation of PAH exposure at a workplace. Even at high exposures metabolic polymorphisms seem to have some effect on biomarker levels, and should be assessed in biomonitoring studies.     

Nutrition,antioxidants, and risk factor profile of nonsmokers,passive smokers and smokers of the Prevention Education Program (PEP) in Nuremberg,Germany

BACKGROUND: An elevated risk for coronary artery disease and lung cancer was reported for smokers and nonsmokers exposed to environmental tobacco smoke. Particularly in nonsmokers, in addition to the adverse effects of tobacco smoke, other factors which are associated with the exposure to environmental tobacco smoke may contribute to the health risks. We investigated both by questionnaires and biochemical analyses whether smokers influence the dietary habits of nonsmokers living in the same household. METHODS: The study population was a subgroup of the Prevention Education Program in Nuremberg: 817 adults aged 27-66 years were allocated to one of the four groups: Nonsmokers living with a nonsmoker (Group 1), nonsmokers living with a smoker (Group 2), smokers living with a nonsmoker (Group 3), and smokers living with a smoker (Group 4). RESULTS: The four groups did not differ in the body mass index, the concentration of lycopene, all-trans-retinol, and selenium in plasma. Plasma concentrations of high-density lipoprotein cholesterol, triglycerides, homocysteine, cobalamin, folate, beta-carotene, and alpha-tocopherol showed a gradient to unfavorable levels from Group 1 to Group 4. This trend was also reflected in the reported dietary intake of beta-carotene, alpha-tocopherol, ascorbic acid, fiber, and linoleic acid. CONCLUSIONS: Our data show that nonsmokers living with smokers indulge in less healthy dietary habits than nonsmokers living with nonsmokers. This has to be considered when evaluating the health risks of exposure to environmental tobacco smoke.     

上海市松江区居民吸烟状况分析

[目的]了解上海市松江区居民的吸烟情况。[方法]在松江地区4个镇1个街道共16万人口中随机选择4772名居民采用统一标准的调查问卷进行入户调查。[结果] 被调查人群中现在吸烟率为23.62％,曾经吸烟率为2.83％,居民现在吸烟率与年龄、性别和文化程度有关P值均<0.01)。开始吸烟的平均年龄为22.59±5.43岁,最主要的原因是好奇、社交需要和解乏。77.3％的现在吸烟者还没有考虑在未来6个月内戒烟。被动吸烟率为65.13％,被动吸烟的场所主要是家中和公共场所。[结论] 松江地区居民的吸烟率低于全国1996年调查的15岁以上人群吸烟率(35.3％)。但松江地区大多数吸烟者尚未考虑戒烟,需要开展有针对性的控烟干预。大多数非吸烟者都受到被动吸烟的危害,有必要采取措施减少在家中和公共场所等地方被动吸烟的机会。     

Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring

This study evaluated the results of several biological methods used simultaneously to monitor coke-oven work. Blood samples from 44 male coke-oven workers and 48 male referents, matched for age and smoking/snuff consumption, were examined for cytogenetic damage in lymphocytes. Urinary thioether excretion was determined for 62, and urine mutagenicity for 31, of the subjects, who followed a standardized diet during the urine sampling. Exposure to polycyclic aromatic hydrocarbons varied with work task, the ambient air levels of benzo[a]pyrene sometimes exceeding 5 micrograms/m3. Cytogenetic damage, urine mutagenicity, and thioether excretion did not differ between the groups. The smokers, however, had significantly higher sister chromatid exchange frequencies, urine mutagenicity, and thioether excretion than the nonsmokers. The absence of biological indications of genotoxic exposure was unexpected and indicates that the studied methods are not adequate to assess the carcinogenic risks of Swedish coke-oven workers.     

Second-hand smoke exposure and blood lead levels in U.S. children

BACKGROUND: Lead is a component of tobacco and tobacco smoke, and smokers have higher blood lead levels than do nonsmokers. METHODS: We examined the relation between second-hand smoke exposure and blood lead levels in a nationally representative sample of 5592 U.S. children, age 4-16 years, who participated in the Third National Health and Nutrition Examination Survey (1988-1994). Linear and logistic regression modeling was used to adjust for known covariates. RESULTS: Geometric mean blood lead levels were 1.5 mug/dL, 1.9 mug/dL, and 2.6 mug/dL for children with low, intermediate, and high cotinine levels, respectively. The adjusted linear regression model showed that geometric mean blood lead levels were 38% higher (95% confidence interval [CI] = 25-52%) in children with high cotinine levels compared with children who had low cotinine levels. The logistic regression models showed that children with high cotinine levels were more likely to have blood lead levels >/=10 mug/dL than were children with low cotinine levels (odds ratio [OR] = 4.4; CI = 1.9-10.5). CONCLUSIONS: Second-hand smoke could be associated with increased blood lead levels in U.S. children aged 4-16 years.     

Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studies: the experience of the MATISS project

To describe serum cotinine levels in a rural Italian population and to examine its usefulness as an epidemiologic biomarker of nicotine exposure, cross-sectional data collected in 1993 for the MATISS Project (2098 men and 1352 women, aged 20–79 years) were used. The study population consisted of 977 current smokers, 882 nonsmokers reporting exposure to environmental tobacco smoke (ETS) and 1520 nonsmokers reporting no ETS exposure. Mean values of serum cotinine measured by radioimmunoassay for never smokers, ex-smokers and current smokers (including four categories of cigarette consumption), and for categories of ETS exposure in all nonsmokers were calculated. In univariate analysis, there was a positive association between self-reported nicotine exposure and serum cotinine levels in all groups. Using self-reported status as truth, sensitivity and specificity for various cotinine cutoff points were estimated to distinguish nonsmokers from smokers. The value of 15 ng/mL represented the best combined levels of sensitivity (95%) and specificity (96%). Using this cutoff point, the overall misclassification rate for self-reported nonsmokers was 2.1% and about two times greater for the more vs. the less educated. In multivariate analysis, reported ETS exposure among nonsmokers was significantly associated with serum cotinine even after adjusting for age, socio-demographic and behavioural factors, though the strength of the association was not strong. In conclusion, serum cotinine represents a reliable epidemiological marker of nicotine intake and may be helpful when studying ETS exposure. Improved information collection is needed to reduce misclassification among nonsmokers and enhance our understanding of the relationship between ETS and cotinine measures.     

Smoking, alcohol, occupation, and hair dye use in cancer of the lower urinary tract

This case-control study was based on 137 Caucasian and 124 Japanese cases of urinary tract cancer identified in Hawaii between 1977 and 1986. Each case was matched on sex, age, and race to two population-based controls. Heavy cigarette smokers (41 or more pack-years for men; 21 or more pack-years for women) had a significantly elevated risk compared with nonsmokers (odds ratio (OR) = 6.2, 95% confidence interval (CI) 3.4-11.1 for the men; OR = 2.8, 95% CI 1.2-6.3 for the women). When the men and women were combined, employment in high-risk industries (includes machinery, automotive, and textiles, among others) was significantly associated with cancer risk (OR = 1.6, 95% CI 1.1-2.3). Alcohol intake and hair dye use showed weaker positive associations with risk that were not statistically significant.     

Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes

BACKGROUND: Free radicals in cigarette smoke may cause oxidative damage to macromolecules, contributing to cardiovascular diseases and cancer. Decreased plasma antioxidant concentrations may indicate cigarette smoke-related oxidative stress. OBJECTIVE: We compared the effects on plasma antioxidant concentrations in cotinine-confirmed active and passive smokers with those in nonsmokers, independent of differences in dietary intakes and other covariates. DESIGN: Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were analyzed for total ascorbic acid, alpha- and gamma-tocopherols, 5 carotenoids, retinol, and cotinine. Groups were compared by using analysis of variance with adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol concentration, fruit and vegetable intakes, and dietary antioxidants. RESULTS: After adjustment for dietary antioxidant intakes and other covariates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro mol/L, respectively). Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than did nonsmokers and passive smokers (ascorbic acid: 43.6, 54.5, and 54.6 micro mol/L, respectively; beta-cryptoxanthin: 0.12, 0.16, and 0.16 micro mol/L, respectively) and significantly lower concentrations of lutein and zeaxanthin than did nonsmokers (0.33 compared with 0.41 micro mol/L). The P values for all the differences described above were < 0.05. No significant differences in plasma concentrations of alpha-tocopherol, alpha-carotene, total carotenoids, lycopene, or retinol were observed. CONCLUSIONS: These results indicate that cigarette smokers and nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than do unexposed nonsmokers, independent of differences in dietary antioxidant intakes. Further research is required to explain why plasma gamma-tocopherol concentrations were significantly higher in smokers and passive smokers than in nonsmokers.     

Elevated blood levels of carcinogens in passive smokers.

The hypothesis that involuntary exposure to tobacco smoke--passive smoking--results in greater risk of cancer was assessed by measuring the levels of two known carcinogens in the blood of 57 nonsmokers with varying degrees of involuntary exposure, including six heavily exposed bartenders. The concentrations of hemoglobin adducts of 4-aminobiphenyl, a bladder carcinogen, were significantly higher in subjects with confirmed involuntary exposure (plasma cotinine concentrations between 2 and 23 ng/ml) compared with subjects with undetectable levels of cotinine. Similarly, adducts of 3-aminobiphenyl were significantly elevated in subjects with confirmed exposure. The odds of 3-aminobiphenyl adduct levels exceeding 2 pg/g of hemoglobin were 6:7 among the confirmed exposed, compared with the odds of 2:42 among subjects with undetectable cotinine (odds ratio = 18; 95 percent confidence interval = 3.3, 94). The validity of the assay was demonstrated by showing striking declines in adduct levels among quitting smokers.     

Cigarette smoking and acute nonlymphocytic leukemia

In a case-control study of acute nonlymphocytic leukemia in western Washington state, cigarette smokers experienced a twofold increased risk of acute nonlymphocytic leukemia compared with nonsmokers. Risk increased significantly with the number of pack-years smoked (p = 0.0008) and decreased with the number of years stopped smoking (p = 0.15). The increased risk in smokers appeared to be limited to those who inhaled into the chest. The authors suggest that further studies of this potential relation are warranted, especially since the prevalence of cigarette smoking is relatively high in our society.     

The effect of paternal smoking on the birthweight of newborns whose mothers did not smoke. Group Health Medical Associates.

We examined the relationship of paternal smoking habits to birthweight in a cohort of infants enrolled at birth (n = 1219). To assess validity of parental smoking reports, cord serum levels of cotinine were measured in 175 newborns. A mean birthweight deficit of 88 g was found in newborns of nonsmoking mothers whose fathers smoked more than 20 cigarettes/day. Only 2 of 138 newborns whose mothers said they were nonsmokers had cotinine levels indicating that their mothers were active smokers. Among infants of nonsmoking mothers, detectability of cotinine in cord blood was significantly correlated with the number of cigarettes smoked daily by fathers. These data suggest that fetal growth may be adversely affected when the mother is passively exposed to tobacco smoke during pregnancy.     

Tobacco smoke exposure and serum cotinine in a random sample of adults living in Verona,Italy

In this study, the authors attempted to validate answers to smoking-habit questions contained in the European Community Respiratory Health Survey questionnaire. The respondents were invited to visit the chest clinic at Verona, Italy, and their serum cotinine levels were measured. The authors invited each of 504 subjects to complete a respiratory interview and to give a blood sample for a radioimmunoassay serum cotinine measurement. A total of 375 subjects responded, of whom 129 were smokers (34.4%), 79 were exsmokers (21.1%), and 167 (44.5%) had never smoked. Exposure to environmental tobacco smoke was reported by 216 subjects (57.6% [mean exposure = 3.8 hr/day (+/- 3.4 hr/day standard deviation)]). In smokers, serum cotinine levels were directly related to the number of cigarettes smoked/day. The authors excluded from analysis nonsmokers who had serum cotinine levels that were > or = 14 ng/ml, and the resulting mean values were 1.7 ng/ml (+/- 2.1 ng/ml standard deviation) in nonsmokers unexposed to environmental tobacco smoke and 2.6 ng/ml (+/- 2.6 ng/ml standard deviation) (p < .002) in nonsmokers exposed to environmental tobacco smoke. There was a relationship between serum cotinine levels and hours of exposure to environmental tobacco smoke (R2 = .136, p < .05). Serum cotinine, which is an objective and accepted measure of tobacco exposure, confirmed the validity of the European Community Respiratory Health Survey questionnaire with respect to smoking habits and environmental tobacco smoke exposure.     

The Usefulness of Periodic Health Examinations

Blood-cadmium (Cd-B) level, blood pressure, and several biological parameters in blood were measured in 440 men who were not occupationally exposed to cadmium and who had a detailed smoking history. No significant correlation was found between Cd-B and blood pressure. Among biological parameters, those known to be related to smoking appeared significantly correlated with Cd-B. Analysis of smoking history showed that Cd-B is strongly elevated in current smokers, with a dose-effect relationship between daily consumption of tobacco and Cd-B; moreover, exsmokers had significantly higher Cd-B than nonsmokers. This finding shows that Cd-B partly reflects past exposure to cadmium.     

Tobacco smoking, pregnancy estrogens, and birth weight

It has been suggested that tobacco smoking during pregnancy reduces birth weight by lowering production rates or levels of total pregnancy estrogens. To evaluate this hypothesis, we examined total estrogen levels by radioimmunoassay in the blood of 141 pregnant women attending the maternity clinic of a major university hospital in Athens during their 26th week of pregnancy. Forty-nine of these women were regular smokers before and during their pregnancy, whereas the remaining 92 had never been regular smokers and did not smoke at all during their pregnancy. Birth weight of offspring was lower among smokers than among nonsmokers by 190.8 g, with a 90% confidence interval of 41.1 to 340.5 g, and higher among women with higher serum estrogen levels (slope b = 1.2 g per 1000 pg/ml with a 90% CI of 0.2 to 2.2 g). There was, however, only a small negative relation between tobacco smoking and serum estrogen levels; in smokers, total estrogen levels were reduced to 91% of the corresponding levels among nonsmokers.     

Cigarette smoking and breast cancer.

An epidemiological case-control study was conducted in New York State, with 1617 primary breast cancer patients and an equal number of controls, to examine the relationship between cigarette smoking and breast cancer. Results showed no overall association between ever smokers versus never smokers and breast cancer risk (odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.90-1.19), nor was there any dose response trend observed with increased levels of smoking. In addition, no association was found with risk and age started smoking, age stopped smoking, amount smoked or total years smoked. Controlling for previously identified risk factors for breast cancer in the analysis did not significantly alter these relationships. Previous studies have found a difference in menopausal age among smokers compared to nonsmokers. The mean menopausal age was only slightly lower in smokers than in never smokers for both cases and controls. Breast cancer risk was observed to be close to unity for premenopausal women (OR = 0.97, 95% CI: 0.74-1.34) and postmenopausal women (OR = 1.06, 95% CI: 0.91-1.26). A recent study suggested breast cancer risk was more strongly related to starting smoking at a young age among women who smoked at least 25 or more cigarettes per day in the most recent year of smoking. This hypothesis was not supported by these data.     

吸烟对精液质量和月经功能的影响

目的 探讨吸烟对精液质量和月经功能的影响. 方法 选择597例男性不育患者精液标本,其中395例为吸烟者,202例为非吸烟者,观察比较2组精液标本的各项参数;女性不生育患者304例,主动吸烟者5例,被动吸烟者198例,不吸烟者101例,分析其月经功能. 结果 吸烟者和非吸烟者相比,精子的正常形态数、精子的密度和精子的活力降低,2组之间差异有统计学意义(P<0.05).女性被动吸烟与女性痛经有显著正相关(P<0.05),女性被动吸烟对月经周期和经期有一定得影响,但差异无统计学意义(P>0.05). 结论 吸烟行为可能与精子的质量下降有关.女性被动吸烟对月经功能造成一定的危害,应引起有关方面的足够重视.     

Passive smoking and lung cancer in nonsmoking women.

OBJECTIVES. The causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case-control study. METHODS. Case patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 lifetime nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from driver's license and Medicare files. RESULTS. No increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all household members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers. CONCLUSIONS. Ours and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoking. Comprehensive actions to limit smoking in public places and worksites are well-advised.     

ERCC2/XPD单核苷酸多态与苯并芘体外诱导DNA加合物损伤的关联性研究

目的评价环境致癌因子苯并芘(B[a]P)所致DNA损伤修复与ERCC2/XPD单核苷酸多态(SNP)的关联。方法收集282例辽宁地区汉族健康人群外周血8ml,常规提取淋巴细胞及DNA,采用Taqman实时定量PCR检测ERCC2/XPDLys751Gln(rs13181),Asp312Asn(rs1799793)和Arg156Arg(rs238406)的基因型;体外培养淋巴细胞,应用B[a]P及S9活化系统,诱导BPDE-DNA加合物的形成;高效液相色谱法检测BPDE-DNA加合物含量;分析BPDE-DNA加合物水平与ERCC2/XPD SNP位点的关联。结果携带ERCC2/XPD Arg156Arg位点AA基因型个体BPDE-DNA加合物水平显著高于CC基因型携带者;50～70岁和≥70岁年龄组人群的加合物水平高于≤30岁年龄组(P<0.05);多元线性回归分析同样显示,ERCC2/XPD Arg156Arg位点SNP及年龄对BPDE-DNA加合物含量的影响有统计学意义(P<0.05)。结论 ERCC2/XPD Arg156Arg位点A等位基因可能与BPDE-DNA加合物的DNA修复能力降低相关联,可能会增加肿瘤易感风险。