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Objectives: The objective of this study was to assess sperm quality and deoxyribonucleic acid (DNA) integrity of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) as compared to control subjects., Material and Methods: The coke oven workers (N = 52) and administrative staff (N = 35) of a steel plant served as the exposed and control groups, respectively. Exposure to PAHs was assessed by measuring 1-hydroxypyren. Analysis of sperm quality (concentration, motility, vitality, and morphology) was performed simultaneously with sperm DNA integrity analysis, including DNA fragmentation, denaturation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo). A questionnaire was conducted to collect demographic and potential confounding data., Results: The coke oven workers had lower percentages of sperm motility, vitality and normal morphology than the control group, but the difference was not significant. For DNA integrity, the coke oven workers had significantly higher concentrations of bulky DNA adducts and 8-oxo-dGuo than the control subjects (p = 0.009 and p = 0.048, respectively). However, DNA fragmentation percentages did not significantly increase as compared to those in the subjects from the control group (p = 0.232). There was no correlation between sperm quality parameters and DNA integrity indicators., Conclusions: Occupational exposure of the coke oven workers to PAHs was associated with decreased sperm DNA integrity. Int J Occup Med Environ Health 2016;29(6):915-926., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Abstract: Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC–MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7–8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo. [Copyright &y& Elsevier]

The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers ( n = 112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel ( n = 67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and sperm chromatin structure assay (SCSA). The PAH-exposed group had a significant increase in bulky DNA adducts and 8-oxo-dGuo compared to the control subjects ( Ps = 0.002 and 0.045, respectively). Coke oven workers’ percentages of DNA fragmentation and denaturation from the PAH-exposed group were not significantly different from those of the control subjects ( Ps = 0.232 and 0.245, respectively). Routine semen parameters and DNA integrity endpoints were not correlated. Concentrations of 8-oxo-dGuo were positively correlated with percentages of DNA fragmentation measured by both TUNEL and SCSA ( Ps = 0.045 and 0.034, respectively). However, the concentrations of 8-oxo-dGuo and percentages of DNA fragmentation did not correlate with concentrations of bulky DNA adducts. In summary, coke oven workers with chronic exposure to PAHs experienced decreased sperm DNA integrity. Oxidative stress could contribute to the degree of DNA fragmentation. Bulky DNA adducts may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Monitoring sperm DNA integrity is recommended as a part of the process of assessing the impact of occupational and environmental toxins on sperm. [ABSTRACT FROM AUTHOR]

Abstract The exposome is a concept that encompasses the totality of internal and external environmental exposures, from conception onwards. Evaluation of the exposome, across the lifecourse represents a significant challenge, e.g., methods/technology may simply not exist to comprehensively assess all exposures, or they may not be applicable to human populations, or may have insufficient sensitivity. Cellular DNA adductomics aims to determine the totality of DNA adducts in the cellular genome. However, application to human populations requires the necessarily invasive sampling of tissue, to obtain sufficient DNA for sensitive analysis, which can represent a logistical and IRB challenge, particularly when investigating vulnerable populations. To circumvent this, we recently applied DNA adductomics to urine, detecting a range of expected and unexpected 2′-deoxyribonucleoside DNA adducts. However, base excision repair, the main DNA repair pathway for non-bulky DNA adducts, and processes such as spontaneous depurination, generate nucleobase adducts. Herein we propose a strategy to simultaneously assess 2′-deoxyribonucleoside and nucleobase adducts, using a widely used mass spectrometic platform (i.e., triple quadrupole tandem mass spectrometry). This will provide a much needed DNA adductomic approach for non-invasively, biomonitoring environmental exposures, through assessing the totality of DNA adducts; contributing to the evaluation of the exposome, across the life-course. Highlights • Evaluation of the exposome, across the lifecourse, is a significant challenge. • DNA adductomics aims to determine the totality of adducts in the genome. • Cellular DNA adductomics invariably requires sampling tissue e.g., blood. • Urinary DNA adductomics non-invasively reflects the body burden totality of adducts. [ABSTRACT FROM AUTHOR]