Stressful events, smoking exposure and other maternal risk factors associated with gestational diabetes mellitus

The incidence of gestational diabetes mellitus (GDM) has increased significantly in the last few decades in the US. Understanding its risk factors is imperative for the prevention of GDM and its sequelae, but the roles of behavioural risk factors such as stressful events and smoking on GDM are generally not well understood. Using data obtained from the New York State (NYS) Pregnancy Risk Assessment Monitoring System survey for 2004-06 and the NYS birth certificates, we examined relationships between GDM, stressful events and smoking among 2690 women who had live singleton births and did not have pre-pregnancy diabetes. After adjustment for risk factors such as maternal age, race/ethnicity, pre-pregnancy body mass index, hypertension, as well as smoking exposure, education, parity, and gestation at first visit for prenatal care, we found that having five or more stressful events 12 months before the baby was born was significantly associated with GDM (OR = 2.49, [95% CI 1.49, 4.16]). In another model, having any stressful event(s) other than 'moved to a new address' 12 months before the baby was born was also moderately associated with GDM (OR = 1.38, [95% CI 1.04, 1.85]). Smoking exposure, assessed by combining maternal smoking and second-hand smoke exposure into six levels, had no significant association with GDM, and did not show a dose-response pattern. The present study suggests that stressful events during pregnancy may be an independent risk factor for GDM. Future studies of GDM should include this common, but potentially modifiable risk factor in analyses.     

Relationship between polycyclic aromatic hydrocarbon-DNA adducts, environmental tobacco smoke, and child development in the World Trade Center cohort

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are air pollutants released by the World Trade Center (WTC) fires and urban combustion sources. BaP-DNA adducts provide a measure of PAH-specific genetic damage, which has been associated with increased risk of adverse birth outcomes and cancer. We previously reported that levels of BaP-DNA adducts in maternal and umbilical cord blood obtained at delivery were elevated among subjects who had resided within 1 mile of the WTC site during the month after 9/11; and that elevated blood adducts in combination with in utero exposure to environmental tobacco smoke (ETS) were significantly associated with decreased fetal growth. OBJECTIVE: Our aim was to assess possible effects of prenatal exposure to WTC pollutants on child development. METHODS: After 11 September 2001, we enrolled a cohort of nonsmoking pregnant women who delivered at three lower Manhattan hospitals. We have followed a subset of children through their third birthdays and measured cognitive and motor development using the Bayley-II Scales of Child Development (BSID-II). RESULTS: In multivariate analyses, we found a significant interaction between cord blood adducts and in utero exposure to ETS on mental development index score at 3 years of age (p = 0.02, n = 98) whereas neither adducts nor ETS alone was a significant predictor of (BSID-II) cognitive development. CONCLUSION: Although limited by small numbers, these results suggest that exposure to elevated levels of PAHs in conjunction with prenatal ETS exposure may have contributed to a modest reduction in cognitive development among cohort children.     

450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy

Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10^–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.     

Knowledge and attitudes of economically disadvantaged women regarding exposure to environmental tobacco smoke: a Michigan,USA study

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is a global public health problem which is particularly acute in groups where smoking rates are higher than in the general population. A study was undertaken to investigate knowledge, attitudes and preventive efforts with regard to exposure to ETS in a sample of economically disadvantaged women residing in Michigan, USA. METHODS: Analysis-of-variance techniques were used to investigate how knowledge, attitudes and preventive efforts regarding exposure to ETS relate to demographic variables such as smoking status, ethnicity, education, employment, and income; and analysis-of-covariance techniques were applied to determine the degree to which knowledge, attitudes, age, smoking status, ethnicity, education, employment, income and home environment predict these women's preventive efforts regarding exposure to ETS. RESULTS: Generally, women with no high school diploma and women who were smokers were less knowledgeable about the adverse health effects of exposure to ETS, had worse attitudes concerning exposure to ETS and were less likely to take preventive steps to limit their exposure to ETS than were women who had more formal education or who were nonsmokers, respectively. The primary predictors of preventive efforts were knowledge, attitudes and smoking status. CONCLUSIONS: The results suggest that educational efforts focusing on increasing knowledge and improving attitudes regarding exposure to ETS, as well as providing practical strategies for limiting exposure to ETS, should be developed and delivered to at-risk populations.     

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns’ health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p < 0.05) and inversely associated with gestational age (p = 0.08; p = 0.02). Structural equation modeling results confirmed a positive association between cotinine and MT-CO1 and2 (p < 0.01) and inverse associations with gestational age (p = 0.02) and IGF-1 (p < 0.01). We identified a dose-dependent increase in the level of MT-CO1 and MT-CO2 associated to increased cord serum cotinine and decreased gestational age.     

In utero exposure to tobacco smoke,subsequent cardiometabolic risks,and metabolic syndrome among U.S. adolescents

Purpose

Maternal smoking during pregnancy increases risk of adverse pregnancy outcomes. However, little is known regarding in utero smoke exposure and offspring cardiometabolic risk. Thus, we examined the association between in utero smoke exposure and cardiometabolic risk factors and the metabolic syndrome (MetS) in adolescents.

The clinical and economic burden of fibromyalgia compared with diabetes mellitus and hypertension among Bedouin women in the Negev

BACKGROUND: Fibromyalgia (FM) is a common idiopathic chronic, widespread pain syndrome with tenderness in anatomically defined tender points. OBJECTIVES: The purpose of the present study was to describe and characterize the economic and daily work burden of FM compared with diabetes mellitus and hypertension. METHODS: A retrospective study was conducted in 2001 in a primary care clinic, the Kuseife clinic of the Clalit Health Services. Data for the three study groups were obtained from the computerized database of the Kuseife clinic and the Negev District, Israel. The study group included 102 FM patients. The control groups included 102 diabetes patients and 103 patients with hypertension. RESULTS: Hospitalization and hospital day care services were the main expenses incurred by patients in this study. There were no differences among the study groups in any cost parameter examined except for the cost of diagnostic tests (P < 0.01), which was less for FM patients. FM patients were referred to specialists and diagnostic procedures more frequently than the control groups. No statistical difference was found in the total number of clinic visits, but FM patients visited physicians more frequently and visited nurses less frequently than patients in the other two groups (P < 0.05). CONCLUSIONS: FM patients consume health care resources to a similar extent to patients with other chronic diseases such as diabetes mellitus and hypertension, but the latter usually receive much more attention from the health care system. Greater awareness of this disorder can improve management and facilitate planning of health care resources, thus improving quality of care.     

Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review

Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern.Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity.Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research recommendations. This review also serves as an introduction to an upcoming series of articles that review the literature regarding specific exposures and outcomes in more detail.     

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming.Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.     

Thyroid hormone status of newborns in relation to in utero exposure to PCBs and hydroxylated PCB metabolites

The associations between in utero exposure to polychlorinated biphenyls (PCBs) or hydroxylated PCB metabolites (OH-PCBs), and free thyroxin (fT4) or thyroid-stimulating hormone (TSH) status in the newborn were investigated as a pilot study of a large-scale epidemiologic study on in utero PCB or OH-PCB exposure and thyroid function of the newborns. Umbilical cord tissue was used as the media for the biological monitoring of PCBs/OH-PCBs exposure in utero. For the measurement of fT4 and TSH, a heel-prick blood sample spotted on filter paper, which is called Guthrie card, is collected from each neonate at day 4-6 postpartum for this study when the mass screening sampling was performed. We showed that the concentration of total OH-PCBs and one of the OH-PCB congeners (OH-PCB 187) was related significantly to higher fT4 level of newborns. On the other hand, the concentration of total PCBs and PCB congeners (PCB 118, 138, 153, and 180) showed no relationship with fT4 and TSH level of the newborns. The results obtained in this pilot study indicated the possibility that in utero OH-PCBs exposure affects thyroid hormone status of newborns.     

Associations between prenatal exposure to polychlorinated biphenyls and neonatal thyroid-stimulating hormone levels in a Mexican-American population, Salinas Valley, California

BACKGROUND: Studies have reported that prenatal exposure to polychlorinated biphenyls (PCBs) may alter neurodevelopment in both humans and animals. Furthermore, prenatal exposure to some PCB congeners and commercial mixtures has been shown to decrease free and total thyroxine (T(4)) blood levels in animals. Because thyroid hormones (TH) are essential for normal neurologic development, it has been suggested that the deleterious neurodevelopmental effect of PCBs may occur through TH disruption. PCBs may in turn affect TH levels by inducing the microsomal enzyme uridinediphosphate glucuronosyltransferase (UDP-GT), which is involved in TH elimination. OBJECTIVES: Our goals were to group PCB congeners based on their potential to induce microsomal enzymes in animals, and to examine the relationship between neonatal TSH levels and prenatal exposure to PCB congeners grouped according to their structure and potential mechanisms of action. METHODS: We measured the concentration of 34 PCB congeners in serum samples collected from 285 pregnant women and the thyroid-stimulating hormone (TSH) levels in their children's blood collected shortly after birth. RESULTS: We found no association between the sum of PCB congeners, the toxic equivalents, or structure-based groupings (mono- or di-ortho substituted congeners), and TSH blood concentration. However, we found a positive association between the sum of congeners suspected to be UDP-GT inducers (more specifically cytochrome P450 2B inducers) in animals and neonatal TSH levels. In individual congener analyses, PCBs 99, 138, 153, 180, 183, 187, 194, and 199 were positively associated with neonatal TSH levels after adjustment for covariates. PCBs 194 and 199 remained significant after adjustment for multiple hypothesis testing. CONCLUSIONS: Our results support grouping PCB congeners based on their potential mechanism of action of enzyme induction when investigating associations with TH. Findings also suggest that PCBs affect TH homeostasis even at the low background level of exposure found in the CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas) population.     

PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero

Background

Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.

Objective

We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.

Methods

We measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds’ blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.

Results

Children with the PON1_−108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1_−108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.

Conclusion

PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.     

Early-Life Exposure to Outdoor Air Pollution and Respiratory Health,Ear Infections,and Eczema in Infants from the INMA Study

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants.Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO₂) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.Results: A 10-µg/m³ increase in average NO₂ during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO₂ were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO₂, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.     

In utero and lactational exposure to PCBs in mice: adult offspring show altered learning and memory depending on Cyp1a2 and Ahr genotypes

Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response.Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs.Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahr^b1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahr^d_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahr^b1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors.Results: We observed the most significant deficits in response to PCB treatment in Ahr^b1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on at least one measure of learning or behavior.Conclusions: High levels of maternal hepatic CYP1A2 offer the most important protection against deficits in learning and memory in offspring exposed to a mixture of coplanar and noncoplanar PCBs. High-affinity AHR is the next most important factor in protection of offspring.     

In utero and lactational exposures to low doses of polybrominated diphenyl ether-47 alter the reproductive system and thyroid gland of female rat offspring

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are capable of disrupting thyroid hormone homeostasis. PBDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is one of the most abundant congeners found in human breast adipose tissue and maternal milk samples. OBJECTIVES: We evaluated the effects of developmental exposure to low doses of PBDE-47 on the female reproductive system. METHODS: Pregnant Wistar rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 microg/kg body weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in the drinking water from GD7 through postnatal day (PND) 21. RESULTS: In female offspring sacrificed on PND38, there was a significant decrease in ovarian weight after exposure to PTU or 140 microg/kg PBDE-47. Alterations in folliculogenesis were apparent: we observed a decrease in tertiary follicles and serum estradiol concentrations in the offspring exposed to either PTU or 700 microg/kg PBDE-47. PTU exposure also resulted in a decrease in primordial follicles. On PND100, persistent effects on the thyroid glands included histologic and morphometric changes after exposure to either PTU or PBDE-47. No relevant changes in reproductive indices were observed after mating the exposed F1 females with nontreated males. CONCLUSIONS: Administration of PBDE-47 at doses relevant to human exposure led to changes in the rat female reproductive system and thyroid gland.     

GDM母体血清HIF-1α、ET-1、尿酸、内脂素的变化与新生儿Apgar评分、体质量的关系

目的 探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)母体血清中缺氧诱导因子1α(hypoxia-inducible factor alpha,HIF-1α)、内皮素-1(endothelin-1,ET-1)、尿酸、内脂素水平的变化及与新生儿Apgar评分、体质量情况的关系。 方法 选取150例GDM孕妇(GDM组)、正常妊娠妇女150例(对照组),收集时间2016年1月－2017年6月,检测并比较两组孕24～28周的血清HIF-1α、ET-1、尿酸、内脂素水平,并随访至分娩结束,观察两组新生儿的分娩结局,探讨上述指标与新生儿结局的关系。 结果 孕24～28周,GDM组的HIF-1α、ET-1、尿酸、内脂素水平显著高于对照组,差异有统计学意义(P<0.05);GDM组和对照组的分娩方式、胎膜早破发生率差异无统计学意义(P>0.05);GDM组的分娩孕周、1 min Apgar评分均显著低于对照组(P<0.05),GDM组新生儿的体质量大于对照组(P<0.05);GDM组孕妇血清HIF-1α、ET-1水平与新生儿的1 min Apgar评分呈显著的负相关关系(P<0.05),GDM组孕妇血清尿酸、内脂素水平与新生儿的体质量呈显著的正相关关系(P<0.05)。 结论 GDM孕妇的HIF-1α、ET-1、尿酸、内脂素水平均升高,并且与新生儿Apgar评分、体质量密切相关。     

Occupational exposure to benzene and chromosomal structural aberrations in the sperm of Chinese men

Background: Benzene is an industrial chemical that causes blood disorders, including acute myeloid leukemia. We previously reported that occupational exposures near the U.S. Occupational Safety and Health Administration permissible exposure limit (8 hr) of 1 ppm was associated with sperm aneuploidy.Objective: We investigated whether occupational exposures near 1 ppm increase the incidence of sperm carrying structural chromosomal aberrations.Methods: We applied a sperm fluorescence in situ hybridization assay to measure frequencies of sperm carrying partial chromosomal duplications or deletions of 1cen or 1p36.3 or breaks within 1cen-1q12 among 30 benzene-exposed and 11 unexposed workers in Tianjin, China, as part of the China Benzene and Sperm Study (C-BASS). Exposed workers were categorized into low-, moderate-, and high-exposure groups based on urinary benzene (medians: 2.9, 11.0, and 110.6 µg/L, respectively). Median air benzene concentrations in the three exposure groups were 1.2, 3.7, and 8.4 ppm, respectively.Results: Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for all structural aberrations combined were 1.42 (95% CI: 1.10, 1.83), 1.44 (95% CI: 1.12, 1.85), and 1.75 (95% CI: 1.36, 2.24) and for deletion of 1p36.3 alone were 4.31 (95% CI: 1.18, 15.78), 6.02 (95% CI: 1.69, 21.39), and 7.88 (95% CI: 2.21, 28.05) for men with low, moderate, and high exposure, respectively, compared with unexposed men. Chromosome breaks were significantly increased in the high-exposure group [IRR 1.49 (95% CI: 1.10, 2.02)].Conclusions: Occupational exposures to benzene were associated with increased incidence of chromosomally defective sperm, raising concerns for worker infertility and spontaneous abortions as well as mental retardation and inherited defects in their children. Our sperm findings point to benzene as a possible risk factor for de novo 1p36 deletion syndrome. Because chromosomal aberrations in sperm can arise from defective stem cells/spermatogonia, our findings raise concerns that occupational exposure to benzene may have persistent reproductive effects in formerly exposed workers.     

Oxidative stress and anxiety-like symptoms related to withdrawal of passive cigarette smoke in mice: beneficial effects of pecan nut shells extract, a by-product of the nut industry

The present study evaluated the role of pecan nut (Carya illinoensis) shells aqueous extract (AE) against oxidative damage induced by cigarette smoke exposure (CSE) and behavioral parameters of smoking withdrawal. Mice were passively exposed to cigarette smoke for 3 weeks (6, 10, and 14 cigarettes/day) and orally treated with AE (25 g/L). CSE induced lipid peroxidation in brain and red blood cells (RBC), increased catalase (CAT) activity in RBC, and decreased plasma ascorbic acid levels. AE prevented oxidative damage and increased antioxidant defenses of mice exposed to cigarette smoke. In addition, AE reduced the locomotor activity and anxiety symptoms induced by smoking withdrawal, and these behavioral parameters showed a positive correlation with RBC lipid peroxidation. Our results showed the beneficial effects of this by-product of the pecan industry, indicating its usefulness in smoking cessation.