| Polycyclic aromatic hydrocarbons (PAHs) are a kind of hydrocarbon compounds that consist of two or more fused aromatic rings. To date, it has been found that PAHs consist of more than 200 kinds of compounds PAHs, including naphthalene, anthracene, phenanthrene and pyrene. PAHs are generated from incomplete combustions of many organic compounds such as coal, petrochemical products, rubber, plastic, wood and tobacco, and have beed detected in the occupational and living environments. PAHs pollution in the environment and their health hazards have attracted a great deal of attention for many decades, because of their carcinogenicy, teratogenicy and mutagenicy. Occupational PAHs exposure is mainly caused by the discharge of a large number of coke oven emissions (COEs) during the coking process. Whereas non-occupational PAHs exposure comes from the pollutants discharge of vehicle exhaust, smoke, coal burning and household cooking process. Although many studies reported adverse effects of occupational PAHs exposure, however, a few studies reported adverse effects of PAHs among the general population. PAHs can be absorbed into the body by lungs, gut, and skin, and be metabolized by cytochrome P450 monooxygenases in the liver into their monohydroxylated metabolites of polycyclic aromatic hydrocarbons (PAHs), of which the metabolites with 2-3 aromatic rings are mainly excreted via the urine and the others are mainly excreted via the fecal. Previous studies reported the urinary polycyclic aromatic hydrocarbon metabolites (OH-PAHs) are considered as effective indicators of recent human exposure to PAHs, thus they are often considered as an internal biomarkers of exposure to PAHs in the envrionment. Urinary 1-hydroxypyrene (1-OHPYR) is the most common marker for estimating individual-level exposure to PAHs. However, urinary 1-hydroxypyrene does not fully reflect PAHs exposure, because pyrene accounts for only 2-10% of total PAHs. Obviously, it has its limition only urinary 1-OHPYR as a marker to estimate PAHs exposure. Therefore, to detect levels of multiple urinary OH-PAHs can more objectively reflect the exposure to PAHs in human body.A large number of reactive oxygen species (ROS) are generated during the metabolic process PAHs. While insufficient scavenging of ROS occure, excessive ROS can attack biological macromolecules, causes oxidative damage, inflammation and even certain diseases. Level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a form of ROS-mediated oxidative DNA damage, therefore, urinary 8-OHdG level often serves as a marker to estimate oxidative DNA damage. Epidemiological studies suggested that the COEs with PAHs caused early damage among workers exposed to high PAHs level in the occupation environment. However, the obtained results are inconsistent among the children and the certain patients in association between exposure to PAHs and oxidative DNA damage. In the present study, the association of environmental background level of exposure to PAHs with the urinary 8-OHdG was investigated among the general population.Diabetes is an envrinment-related disease. It is characterized by chronic high blood sugar metabolic disorders, accompaning with abnormal metabolisms of sugar, fat and proteins due to insufficient insulin secretion and/or functional defect. In recent years, the prevalence of Type 2 diabetes mellitus has rapidly increased in urban residents in China. Numerous studies have found that many factors are associated with diabetes, including genetic factror, obesity, overnutrition, sedentary lifestyle, smoking and chronic exposure to low concentration of arsenic trioxide and organic pesticides. Additionally, exposure to PAHs can cause oxidative stress and systemic inflammation in the human body, and then induce insulin resistance and ultimately lead to diabetes. The study aimed to investigated associations between non-occupational exposure to PAHs and diabetes in a Chinese adult population, and provide scientific basic data for diabetes comprehensive prevention and control.Part One Baseline levels of urinary OH-PAHs and their influencing factors in the population from the Wuhan-Zhuhai corhort[Objectives] Urinary OH-PAHs levels and their influencing factors were investigated in the adults.[Methods] Among population (n=4812) from the Wuhan-Zhuhai (WHZH) Cohort Study,4347 participants were included in the first part of this study. They provided the urine samples for measurements of urinary OH-PAHs test and urinary creatinine test. Levels of 12 kinds of urinary OH-PAHs were measured by gas chromatography-mass spectrometry, including urinary 1-hydroxynaphthalene, 2-hydroxynaphthalene,2-hydroxyfluorene,9-hydroxyfluorene, 1-hydroxyphenanthrene,2-hydroxyphenanthrene,3-hydroxyphenanthrene, 4-hydroxyphenanthrene,9-hydroxyphenanthrene,1-hydroxypyrene,6-hydroxyflexor and 3-hydroxybenzopyrene. As urinary 6-hydroxyflexor and 3-hydroxybenzopyrene levels in more than 80% of the samples were below the corresponding detection limits, these two kinds of urinary OH-PAHs were excluded in the analysis. Urinary creatinine concentrations were measured by an automatic biochemistry analyzer and used to correct urinary OH-PAHs levels. The normal distributions of the study variables were determined by One-Sample Kolmogorov-Smirnov Test. Differences in urinary OH-PAHs levels in the participants from Wuhan and Zhuhai cities were analyzed by Mann-Whitney Test, and then urinary OH-PAHs levels in the participants from the two cities were compared with those in the population from the NHANES Cohort. Differences in the continuous and categorical variables between the participants from the two cities were compared by Studen t test and ?2 test, respectively. Multivariate linear regression analysis was used to analyze affecting factors for urinary OH-PAHs levels after adjusted for sex, age, active and passive smoking, drinking, exercise, self-cooking meals, kitchen ventilation, eating habits, body mass index (BMI), hypertention and hyperelipidemia.[Results] The result showed that ?among all paricipants from the two cities, the propotions of 10 kinds of urinary OH-PAHs (without creatinine correction) accounting for the total urinary OH-PAHs concentration were:33.31% for hydroxynaphthalene,25.44% for hydroxyfluorene,31.80% for hydroxyphenanthrene and 9.45% for hydroxypyrene. Greater propertions of urinary 2-hydroxynaphthalene (25.51%) and 9-hydroxyfluorene (21.00%) were found compared to other OH-PAHs accouting for total urinary OH-PAHs. Median levels (without creatinine correction) of urinary 2-hydroxynaphthalene (12.15?g/l) and 9-hydroxyfluorene (10.56?g/l) in Wuhan residents were higher compared to Zhuhai ones (10.46?g/l for urinary 2-hydroxynaphthalene,8.27?g/l for 9-hydroxyfluorene. With the exception of urinary 1-hydroxyphenanthrene and 1-hydroxypyrene, other urinary OH-PAHs levels (without creatinine correction) in Wuhan residents were higher compared to Zhuhai ones (P<0.01);?among all paricipants from the two cities, the propotions of 10 kinds of urinary OH-PAHs (creatinine correction) accounting for total urinary OH-PAHs concentration were:29.15% for hydroxynaphthalene,25.23% for hydroxyfluorene, 36.26% for hydroxyphenanthrene and 9.36% for hydroxypyrene. Greater propertions of urinary 2-hydroxynaphthalene (22.25%) and 9-hydroxyfluorene (20.96%) were found compared to other OH-PAHs accouting for total urinary OH-PAHs. Median levels (creatinine correction) of urinary 2-hydroxynaphthalene (1.14?g/mmol Cr) and 9-hydroxyfluorene (0.93?g/mmol Cr) in Wuhan residents were higher compared to Zhuhai ones (0.85?g/mmol Cr for urinary 2-hydroxynaphthalene and 0.65?g/mmol Cr for 9-hydroxyfluorene. With the exception of urinary 1-hydroxypyrene, significant differences in other urinary OH-PAHs levels (creatinine correction) were found between the urban residents from the two cities (P<0.01 or P<0.05), and the other urinary OH-PAHs levels (creatinine correction) in Wuhan residents were higher than those in the Zhuhai residents except for urinary 1-hydroxyphenanthrene;?compared with the geometric mean concentration (without creatinine correction) of urinary OH-PAHs in population from the United States NHANES Cohort, the geometric mean concentrations of urinary OH-PAHs (including 1-hydroxynaphthalene, 2-hydroxynaphthalene,2-hydroxyfluorene,9-hydroxyfluorene, 1-hydroxyphenanthrene,2-hydroxyethyphenanthrene,3-hydroxypropyphenanthrene, 4-hydroxypropyphenanthrene,9-hydroxypropyphenanthrene and 1-hydroxpyrene) in Wuhan residents were 3.12,5.48,10.09,51.96,18.47,34.39,35.45,83.49,219.44 and174.04 times higher than those in the population of the NHANES Cohort, respectively. The geometric mean concentrations (without creatinine correction) of the detected urinary OH-PAHs (10 kinds of OH-PAHs) in Zhuhai residents were 2.31, 4.62,8.91,35.91,30.27,23.86,15.00,63.49,150.56 and 198.51 times higher than those in the population of the NHANES Cohort, respectively. The geometric mean concentrations (creatinine correction) of urinary OH-PAHs (including 1-hydroxynaphthalene,2-hydroxynaphthalene,2-hydroxyfluorene,9-hydroxyfluorene, 1-hydroxyphenanthrene,2-hydroxyethyphenanthrene,3-hydroxypropyphenanthrene, 4-hydroxypropyphenanthrene,9-hydroxypropyphenanthrene and 1-hydroxpyrene) in Wuhan residents were 2.56,4.46,8.27,41.80,15.16,27.84,30.37,66.85,179.44 and 139.50 times higher than those in the population of the NHANES Cohort, respectively. The geometric mean concentrations (creatinine correction) of the detected urinary OH-PAHs (10 kinds of urinary OH-PAHs) in Zhuhai residents were 1.75,3.49,6.85, 26.93,23.37,18.01,11.61,47.44,171.63 and 147.36 times higher than those in the population of the NHANES Cohort;?the results of multiple linear regression analysis suggest that in Wuhan residents, sex, age, active smoking, intake frequency of grains (times per month), body mass index (BMI) and high-density lipoprotein (HDL) were affecting factors for the sum of urinary hydroxynaphthalene (P<0.01 or P<0.05), sex, age, kitchen ventilation, intake frequency of grains (times per month), BMI, HDL, red blood cell (RBC) and heart rate for the sum of urinary hydroxyfluorene levels (P<0.01 or P<0.05), sex, age, intake frequency of grains and fish (times per month), BMI, hyperlipidemia, diabetes, HDL, RBC and heart rate for the the sum of urinary hydroxyphenanthrene levels (P<0.01 or P<0.05), sex, age, smoking, platelet (PLT) and heart rate for urinary 1-hydroxypyrene levels (P<0.01 or P<0.05), sex, age, smoking status, kitchen ventilation, intake frequency of grains (times per month), BMI, HDL, RBC and heart rate for the sum of urinary OH-PAHs levels (P<0.01 or P<0.05); in Zhuhai residents, sex, BMI, HDL and RBC were the affecting factors for the sum of urinary hydroxynaphthalene (P<0.01 or P<0.05), sex, intake frequency of salted and smoked food (times per month), BMI, LDL and heart rate for the sum of urinary hydroxyfluorene levels (P<0.01 or P<0.05), sex, passive smoking, kitchen ventilation, intake frequency of grains, fish and salted and smoked food (times per month), RBC and heart rate for the sum of urinary hydroxyphenanthrene levels (P<0.01 or P<0.05), sex, drinking status, LDL and heart rate for urinary 1-hydroxypyrene levels (P<0.01 or P<0.05), sex, BMI, passive smoking, intake frequency of grains and salted and smoked food (times per month), HDL, RBC and heart rate for the sum of urinary OH-PAHs levels (P<0.01 or P<0.05).[Conclusions] Urinary OH-PAHs levels in the residents from the two cities were higher than those in the population of the NHANES Corhort, particularly, the sum concentrations of urinary hydroxyphenanthrene and hydroxypyrene were relative higher compared to the NHANES Corhort population. The differences in levels of 9 kinds of urinary OH-PAHs in the urban residents from the two cities were found. Additionally, differences in factors affecting urinary OH-PAHs levels were found between the residents from the two cities.Part Two Associations of urinary OH-PAHs levels and urinary 8-OHdG levels[Objectives] Associations between urinary OH-PAHs levels and urinary 8-OHdG levels were investigated.[Methods] Among the Wuhan residents (n=3053) from the Wuhan-Zhuhai (WHZH) Study Cohort (n=4812),2548 individuals with data on urinary OH-PAHs, urinary 8-OHdG test and urinary creatinine levels were included this study. Considering factors affecting levels urinary OH-PAHs and urinary 8-OHdG, individuals (n=674) with diabetes, cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, emphysema, hepatitis and nephritis were excluded, finally 1874 ones were included in the second part of this study. Levels of urinary 8-OHdG were measured by high performance liquid chromatography-electrochemical detection methods. The statistical methods describled in the first part of this study were used.[Results] The result showed that ?levels of urinary OH-PAHs (including 2-hydroxynaphthalene,9-hydroxyfluorene,1-hydroxyphenanthrene, 2-hydroxyphenanthrene,3-hydroxyphenanthrene,4-hydroxyphenanthrene, 9-hydroxyphenanthrene,1-hydroxypyrene), ?OH-PAHs and urinary 8-OHdG in the females were higher than those in the males (P<0.01);?the results of multivariate logistic regression analysis showed that, the detected urinary OH-PAHs (10 kinds of urinary OH-PAHs) and ?OH-PAHs levels presented a clear dose-response relationship with increased urinary 8-OHdG levels (Ptrend<0.01);?among either the males, active smokers,or individuals without self-cooking meals, a positive association was found between levels of urinary hydroxyfluorene, hydroxyphenanthrene,1-hydroxypyrene or ?OH-PAHs and urinary 8-OHdG levels (Ptrend<0.01); among either the females, non-smokers, individuals with self-cooking meals or individuals with normal weight (BMI<24), levels of urinary hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene or ?OH-PAHs were positively associated with urinary 8-OHdG levels (Ptrend<0.01 or Ptrend<0.05); levels of each kind of urinary OH-PAHs and urinary ?OH-PAHs were positively associated with urinary 8-OHdG level in overweight individuals (BMI?24, Ptrend<0.01 or Ptrend<0.05).[Conclusions] We observed a significant dose-response relationship between levels of each kind of urinary OH-PAHs and urinary 8-OHdG level in the Wuhan residents.Part Three Associations between urinary OH-PAHs, urinary 8-OHdG and diabetes[Objectives] Associations between urinary OH-PAHs levels, urinary 8-OHdG levels and diabetes in Wuhan residents were investigated, to provide a scientific basis for the comprehensive prevention and control of diabetes.[Methods] Among Wuhan residents (n=3053) from the Wuhan-Zhuhai (WHZH) Cohort Study (n=4812),2548 individuals provided the urine samples for measurements of urinary OH-PAHs, urinary 8-OHdG and urinary creatinine. Considering factors affecting levels of urinary OH-PAHs and urinary 8-OHdG, individuals (n=273) with cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, emphysema, hepatitis and nephritis were excluded, finally 2275 ones were included in the third part of this study. Statistical methods described in the first part were used.[Results] The result showed that ?positive assoications was found between levels of each kind of the detected urinary OH-PAHs and urinary ?OH-PAHs (P<0.01), as well as between each kinds of the detected urinary OH-PAHs, urinary ?OH-PAHs and urinary 8-OHdG (P<0.01); Additionally, levels of urinary 1-hydroxyphenanthrene, 2-hydroxyphenanthrene,3-hydroxyphenanthrene,4-hydroxyphenanthrene, 9-hydroxyphenanthrene and 1-hydroxypyrene were positively associated with blood glucose level (P<0.01 or P<0.05); but urinary 8-OHdG level was negatively associated with it (P<0.01);?levels of urinary 2-hydroxynaphthalene, 2-hydroxyfluorene,9-hydroxyfluorene,1-hydroxy phenanthrene, 2-hydroxyphenanthrene,3-hydroxyphenanthrene,4-hydroxy phenanthrene, 9-hydroxyphenanthrene and urinary ?OH-PAHs were higher in diabetic individuals compared to non-diabetic ones (P<0.01 or P<0.05);?adjusted for sex, age, active and passive smoking, drinking, exercise, self-cooking, eating habits, BMI, hypertension and hyperlipidemia, blood glucose level significantly increased with increased urinary 1-hydroxypyrene in non-diabetic individuals; (Ptrend<0.01) and with increased urinary 2-hydroxyphenanthrene in diabetic individuals (Ptrend<0.05);? adjusted for sex, age, active and passive smoking, drinking, exercise, self-cooking meals, eating habits, BMI, hypertention and hyperelipidemia, multiple linear regression analysis showed that, increasing the amount of urinary 8-OHdG in relation to each kind of urinary OH-PAHs or ?OH-PAHs in Wuhan residents with diabetes were higher compared to in ones without diabetes, and with increased levels of urinary 1-hydroxynaphthalene,2-hydroxynaphthalene,2-hydroxyfluorene, 9-hydroxyfluorene,1-hydroxyphenanthrene,3-hydroxyphenanthrene, 4-hydroxyphenanthrene,9-hydroxyphenanthrene,1-hydroxypyrene or ?OH-PAHs; urinary 8-OHdG levels obviously increased in Wuhan residents with diabetes, particularlly, urinary hydroxyphenanthrene and urinary ?OH-PAHs levels markerly affected increased amount of urianry 8-OHdG level; ?mdjusted for sex, age, active and passive smoking, drinking, exercise, self-cooking meals, eating habits, BMI, hypertention and hyperelipidemia, urinary 2-hydroxynaphthalene (OR=1.71,95% CI: 1.01-2.89),1-hydroxyphenanthrene (OR=.06,95%CI:1.15-3.71) and 4-hydroxyphenanthrene (OR=2.03,95%CI:1.19-3.47) were associated with diabetes; after adjusted for the confounders mentioned above plus urinary 8-OHdG, urinary 1-hydroxyphenanthrene (OR=2.03,95%CI:1.12-3.68) and 4-hydroxyphenanthrene (OR=2.00,95%:1.16-3.45) were associated with diabetes.[Conclusions] Urinary 1-hydroxyphenanthrene and 4-hydroxyphenanthrene levels were associated with diabetes in Wuhan residents. |
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