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The concept of the exposome is the encompassing of all the environmental exposures, both exogenous and endogenous, across the life course. Many, if not all, of these exposures can result in the generation of reactive species, and/or the modulation of cellular processes, that can lead to a breadth of modifications of DNA, the nature of which may be used to infer their origin. Because of their role in cell function, such modifications have been associated with various major human diseases, including cancer, and so their assessment is crucial. Historically, most methods have been able to only measure one or a few DNA modifications at a time, limiting the information available. With the development of DNA adductomics, which aims to determine the totality of DNA modifications, a far more comprehensive picture of the DNA adduct burden can be gained. Importantly, DNA adductomics can facilitate a "top-down" investigative approach whereby patterns of adducts may be used to trace and identify the originating exposure source. This, together with other 'omic approaches, represents a major tool for unraveling the complexities of the exposome and hence allow a better a understanding of the environmental origins of disease. [ABSTRACT FROM AUTHOR]

A cross-sectional study was conducted to assess whether urinary 1-hydroxypyrene (1-OHP) could serve as a biomarker to assess the effect of PAHs on cellular and molecular changes of sperm. Urine and semen samples were collected from a total of 65 healthy coke oven workers. Sperm quality parameters (concentration, motility, vitality, and morphology) and semen integrity (DNA fragmentation, 8-oxodGuo, bulky DNA adducts) were analyzed. Sixteen (16) targeted PAHs at the personal breathing zone area were monitored and quantified. Results showed that urinary 1-OHP positively correlated with measured levels of 16 targeted PAHs. Urinary 1-OHP did not significantly correlate with semen quality; however, PAHs with heavy molecular weight, e.g., benzo(g,h,i)perylene and benzo(k)fluoranthene, negatively correlated with morphology and motility of sperms (p = 0.02 and 0.002, p = 0.04 and 0.04, respectively). Urinary 1-OHP positively correlated with the level of 8-oxodGuo and bulky DNA adducts, but not DNA fragmentation. Urinary 1-OHP was a suitable biomarker for an estimate of biologically effective doses of PAH exposure. However, urinary 1-OHP may not be sufficient as a biomarker to assess both cellular and molecular changes of sperm induced by PAHs. [ABSTRACT FROM PUBLISHER]

Skin melanisation ranges widely across human populations. Melanin has antioxidant properties and also acts as a filter to solar ultraviolet radiation (UVR) incident upon the skin. In this study we firstly examined whether melanin level might influence baseline levels of systemic oxidative stress, in 65 humans in vivo from the same geographical area ranging from the lightest to darkest skin type (phototype I-VI). This was examined in winter-time (latitude 53.5°N). Remarkably, we found that urinary biomarkers of oxidatively-generated DNA damage (8-oxodG) and RNA damage (8-oxoGuo) were significantly correlated with skin lightness (L*), such that 14–15% of the variation in their baseline levels could be explained by skin colour. Next we exposed 15 humans at the extremes of skin melanisation to a simulated summer-time exposure of solar UVR (95% UVA, 5% UVB; dose standardised to sunburn threshold), following which they provided a sample of every urine void over the next five days. We found that UVR induced a small but significant increase in urinary 8-oxodG and 8-oxoGuo, with differing kinetics between skin types. Thus greater melanisation is associated with protection against systemic oxidative stress, which may reflect melanin's antioxidant properties, and solar UVR exposure also influences systemic oxidative stress levels in humans. These novel findings may have profound implications for human physiology and health. Image 1 • Biomarkers of systemic oxidative stress correlate with human skin lightness level. • Skin colour contributes 14–15% variation in baseline urinary 8-oxodG and 8-oxoGuo. • UVR exposure of the skin elevates biomarkers of systemic oxidative stress. • Both oxidatively-damaged DNA (8-oxodG) and RNA (8-oxoGuo) increase post-UVR. • Kinetics of urinary biomarker responses following UVR differ between skin types. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease that predominantly affects women of childbearing age and results in various adverse pregnancy outcomes (APOs). Pregnancy was formerly discouraged in patients with SLE because of unstable disease activity during the gestation period, increased thrombosis risk, severe organ damage, and inevitable side effects of immunosuppressive agents. Currently, most patients with SLE have successful pregnancies due to preconception counselling, strict monitoring, and improved therapy with minimised complications for both the mother and foetus. Hydroxychloroquine (HCQ) is extensively used and is beneficial for improving pregnancy outcomes. However, pregnant women with SLE have a high-risk of APOs, such as disease flare, preterm birth, intrauterine growth restriction (IUGR), preeclampsia, and pregnancy loss. Better understanding of the changes in maternal immunity and serum biomarkers, as well as their relationships with SLE-related APOs progression, would facilitate the investigation of molecular mechanisms for triggering and ameliorating APOs. Furthermore, it would enable us to explore and develop novel and effective therapeutic strategies to prevent disease activation. Therefore, this review briefly introduces the interaction between pregnancy outcomes and SLE, elucidates pathophysiological and immunological changes during SLE pregnancy. Furthermore, this review systematically expounds on the effective predictors of APOs and the molecular mechanisms underlying the SLE-related APOs to provide a solid foundation for the advanced management of lupus pregnancy. • SLE has a predominant effect on childbearing-age women and results in various APOs involving with mother and foetus. • Several biomarkers can be applied for predicting APOs during SLE pregnancy. • It is worth noting that multiple driving forces can aggravate APOs progression during SLE pregnancy. • Increasing medicines have been extensively used to relive SLE-related APOs. • Clinical management is required for inhibiting complications of SLE pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Background: 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is the most frequently measured biomarker of oxidative stress. Chromatographic-based methods for 8-oxodGuo in urine are well established; however, the 8-oxodGuo measurement in plasma and saliva has been problematic. Methods: We firstly and successfully applied an on-line solid-phase extraction (SPE) LC-MS/MS following manual SPE pretreatment to quantify the 8-oxodGuo both in plasma and saliva. Urine, plasma and saliva specimens were simultaneously collected from 50 healthy adults and measured for 8-oxodGuo. Results: Mean baseline levels of 8-oxodGuo in plasma and saliva were 21.7±9.2 and 5.1±2.6pg/ml, respectively, being far lower than that in urine (6.2±4.8ng/ml). The 8-oxodGuo levels obtained in this study for plasma and saliva were, however, up to several hundred times lower than those reported by commercial ELISA kit in the literature. Furthermore, the 8-oxodGuo levels in plasma and saliva were significantly correlated with the 8-oxodGuo levels in urine (Spearman correlation coefficients, r =0.33, P =0.02 for plasma and r =0.56, P =0.0015 for saliva). 8-OxodGuo in plasma was also correlated with the 8-oxodGuo in saliva (r =0.52, P =0.0041). Conclusions: Significantly correlations were observed between plasma, saliva and urine, giving the possibility of using other body fluids in addition to urine for assessing whole body oxidative stress. [Copyright &y& Elsevier]

Abstract: We measured the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), a useful biomarker of oxidative injury, in liver (or urine) of maternal mice and their offspring, that were treated with humic acid (HA) and arsenic (As) alone, or their combination during pregnancy. A highly sensitive and specific isotope-dilution LC–MS/MS method was used for 8-oxodGuo quantification. Total arsenic accumulated in the offspring was also measured using ICP–MS. This study demonstrated, for the first time in an animal model, that HA alone treatment led to a significant increase of 8-oxodGuo levels both in liver and urine of maternal mice. No enhanced effect was observed when HA was combined with As, compared with the As alone treatment. With regard to the associated offspring, elevated levels of 8-oxodGuo and total arsenic were observed in offspring only when mother mice were treated with As and its combination with HA, but not for the HA-treated alone. It was worthy to note that the offspring from maternal combined treatment with HA and As had a significantly lower 8-oxodGuo than those of maternal treatment with As alone. This could be explained by that part of As formed complexes with HA and these macromolecules of HA–As complexes may not readily cross the placenta to the fetus, as evidenced by the lower accumulated total As observed in the offspring livers. Overall, it seems that HA may be detrimental to the maternal mice, but in the meantime it can be beneficial to the offspring by reducing free As. [Copyright &y& Elsevier]