The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

:Rationale/ Objectives: The model traffic-related air pollutant exposure, diesel exhaust inhalation, is associated with vascular dysfunction. We studied whether healthy subjects exposed to diesel exhaust exhibit acute vasoconstriction and whether this effect could be modified by the use of antioxidants or by common variants in the angiotensin II type 1 receptor (AGTR1) and other candidate genes.

METHODS:In a genotype- stratified double-blind, four-way crossover study, 22 healthy adult participants were exposed in randomized, balanced order to exposure with diesel exhaust (200μg/m3 PM2.5) and filtered air and to pretreatment with antioxidants (N- acetyl cysteine and ascorbate) and placebo. Before and after each exposure, brachial artery diameter was assessed using ultrasound. Changes in brachial artery diameter were compared across pretreatment and exposure sessions. Gene-exposure interactions were evaluated in the AGTR1 A1166C polymorphism, on which recruitment was stratified, and other candidate genes including TRPV1 and GSTM1.

MAIN RESULTS:Compared with filtered air, exposure to diesel exhaust resulted in a significant reduction in brachial artery diameter (mean -0.09mm, 95% CI -0.01, -0.17; p = 0.03). Pretreatment with antioxidants augmented diesel exhaust related vasoconstriction; participants pretreated with antioxidants had a diesel exhaust effect of -0.18mm (95%CI -0.28 to -0.07 mm; p = 0.01). Diesel exhaust related vasoconstriction was primarily observed in the variant alleles of AGTR1 and TRPV1.

CONCLUSION:We confirmed that short-term exposure to diesel exhaust in healthy participants is associated with acute vasoconstriction in a conductance artery, and found suggestive evidence of involvement of nociception and renin-angiotensin systems in this effect. Pretreatment with an antioxidant regimen increased vasoconstriction. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00434005.

Air pollution is a major social, economic, and health problem around the world. Children are particularly susceptible to the negative effects of air pollution due to their immaturity and excessive growth and development. The aims of this narrative review were to: (1) summarize evidence about the protective effects of breastfeeding on the adverse health effects of air pollution exposure, (2) define and describe the potential mechanisms underlying the protective effects of breastfeeding, and (3) examine the potential effects of air pollution on breastmilk composition and lactation. A literature search was conducted using electronic databases. Existing evidence suggests that breastfeeding has a protective effect on adverse outcomes of indoor and outdoor air pollution exposure in respiratory (infections, lung function, asthma symptoms) and immune (allergic, nervous and cardiovascular) systems, as well as under-five mortality in both developing and developed countries. However, some studies reported no protective effect of breastfeeding or even negative effects of breastfeeding for under-five mortality. Several possible mechanisms of the breastfeeding protective effect were proposed, including the beneficial influence of breastfeeding on immune, respiratory, and nervous systems, which are related to the immunomodulatory, anti-inflammatory, anti-oxidant, and neuroprotective properties of breastmilk. Breastmilk components responsible for its protective effect against air pollutants exposure may be long chain polyunsaturated fatty acids (LC PUFA), antioxidant vitamins, carotenoids, flavonoids, immunoglobins, and cytokines, some of which have concentrations that are diet-dependent. However, maternal exposure to air pollution is related to increased breastmilk concentrations of pollutants (e.g., Polycyclic aromatic hydrocarbons (PAHs) or heavy metals in particulate matter (PM)). Nonetheless, environmental studies have confirmed that breastmilk's protective effects outweigh its potential health risk to the infant. Mothers should be encouraged and supported to breastfeed their infants due to its unique health benefits, as well as its limited ecological footprint, which is associated with decreased waste production and the emission of pollutants.

INTRODUCTION:One of the main functions of cutaneous tissues is to protect our body from the outdoor insults. Ozone (O3) is among the most toxic stressors to which we are continuously exposed and because of its critical location, the skin is one of the most susceptible tissues to the oxidative damaging effect of O3. O3 is not able to penetrate the skin, and although it is not a radical per se, the damage is mainly a consequence of its ability to induce oxidative stress via the formation of lipid peroxidation products.

AIM OF STUDY:In this study we investigated the protective effect of defined"antioxidant"mixtures against O3 induced oxidative stress damage in human keratinocytes and understand their underlying mechanism of action.

RESULTS:Results showed that the mixtures tested were able to protect human keratinocytes from O3-induced cytotoxicity, inhibition of cellular proliferation, decrease the formation of HNE protein adducts, ROS, and carbonyls levels. Furthermore, we have observed the decreased activation of the redox sensitive transcription factor NF-kB, which is involved in transcribing pro-inflammatory cytokines and therefore constitutes one of the main players associated with O3 induced skin inflammation. Cells exposed to O3 demonstrated a dose dependent increase in p65 subunit nuclear expression as a marker of NF-kB activation, while pre-treatment with the mixtures abolished NF-kB nuclear translocation. In addition, a significant activation of Nrf2 in keratinocytes treated with the mixtures was also observed.

CONCLUSION:Overall this study was able to demonstrate a protective effect of the tested compounds versus O3-induced cell damage in human keratinocytes. Pre-treatment with the tested compounds significantly reduced the oxidative damage induced by O3 exposure and this protective effect was correlated to the abolishment of NF-kB nuclear translocation, as well as activation of Nrf2 nuclear translocation activating the downstream defence enzymes involved in cellular detoxification process.