Environews
NIEHS NEWS | NIH Launches Genes and Environment Initiative
Researchers and clinicians agree that one of the best ways to combat maladies such as asthma, arthritis, and Alzheimer disease is to uncover their causes and prevent them before they happen. Now the NIEHS is poised to join the new NIH Genes and Environment Initiative, described in this article (p. A220). The multimillion-dollar effort will use genotyping studies and innovative environmental monitoring tests and devices to shed new light on the relationship between genes, the environment, and human health.
FOCUS | Ports in a Storm
Ports have long functioned as international gateways, allowing us to share goods from one corner of the world to another. Statistics show that this form of commerce still accounts for the highest percentage of traded goods, and continues to grow. But along with this steady growth has come an unfortunate side effect: extensive pollution. This article (p. A222) details how port pollution affects human health and looks at what's being done to get those pollution levels under control.
SPHERES OF INFLUENCE | Unfair Trade: E-Waste in Africa
Several African nations engage in a thriving used electronics industry, with the used equipment imported mostly from the United States. But with few regulations in place to limit the recycled electronics shipped, these countries face with an increasing amount of obsolete electronic junk and no safe way to dispose of it. This article (p. A232) looks at how the trend of shipping used electronics to Africa is delivering needed technology but also leaving Africa to wade through a growing accumulation of e-waste.
INNOVATIONS | Safe Harbor: Protecting Ports with Shipboard Fuel Cells
With air pollution in port cities reaching health-threatening levels because of the diesel fuel used by docked ships, it's clear there is a need for an alternative fuel source that's easier on the air. One possible answer: energy derived from fuel cell technology. This article (p. A236) examines this emerging fuel source, which offers cleaner, more efficient energy.
Review
IMMUNOLOGY | Perinatal Immunotoxicity and Children's Health
The developing immune system undergoes dynamic changes and is a sensitive toxicologic target for environmental chemicals and drugs. However, safety evaluation has relied almost exclusively upon exposure of adults to predict perinatal immune risk. Dietert and Piepenbrink (p. 477) discuss the reasons why immunotoxic assessment is important for current childhood diseases and why adult exposure assessment cannot predict the effect of xenobiotics on the developing immune system. The authors provide examples of developmental immunotoxicants for which age-based risk appears to differ, and stress the need to replace adult exposure assessment with protocols that can protect the developing immune system.
Research
TOXICOLOGY | Use of Monensin in the Treatment of Lead Intoxication
Among divalent cations, the ionophore monensin shows high activity and selectivity for the transport of lead ions (Pb2+) across phospholipid membranes. Hamidinia et al. (p. 484) demonstrate that monensin significantly increases the amount of Pb removed from femur, brain, and heart when coadministered to rats receiving meso-dimercaptosuccinate for treatment of Pb intoxication. The authors found an increase in Pb removal from liver and kidney but no similar effect in skeletal muscle. Monensin may act by cotransporting Pb2+ and OH- ions out of cells in exchange for external sodium ions and be particularly useful when applied in combination with hydrophilic Pb2+ chelators.
BIOMARKERS | Toluene Induces CYP2E1 mRNA in Lymphocytes
Print workers are exposed to organic solvents, and the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Mendoza-Cantú et al. (p. 494) investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone/chlorzoxazone quotient in plasma, and the role of genotype in these workers. Genotype did not alter the association between toluene exposure ratio and mRNA content. CYP2E1 mRNA content in could be a sensitive and noninvasive biomarker useful for monitoring exposed persons.
ENVIRONMENTAL TOXICOLOGY | Brain Aromatase and Sex Reversal in EDC Mixtures
Exposure of fish to estrogen or estrogen-mimicking chemicals (xenoestrogens) during a critical period of development can irreversibly invert sex differentiation. Kuhl and Brouwer (p. 500) examine the role brain aromatase plays in the genesis of developmental abnormalities in response to endocrine-disrupting chemicals (EDCs). The effects of a mixture of antagonistic and environmentally relevant EDCs on development were examined to determine if their combined actions could lessen each other's impacts. The observation that estradiol biosynthesis inhibitors do not block the effect of the xenoestrogen suggests that, in the environment, exposure to seemingly antagonistic EDCs does not necessarily lessen the harmful impacts of these compounds.
SIGNAL TRANSDUCTION | Lead Increases LPS-Induced Liver Damage
Lead and lipopolysaccharide (LPS) are important environmental pollutants that activate cells through different receptors and participate in distinct upstream signaling pathways. Pb increases the amount of LPS-induced tumor necrosis factor- (TNF-). Cheng et al. (p. 507) examined the cells responsible for the excess production of Pb-increased LPS-induced TNF- and liver injury, and the roles of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (MAPK) in the induction of TNF-. Monocytes and macrophages were the cells primarily responsible for producing, through the PKC/MAPK pathway, the excess Pb-increased LPS-induced TNF- that caused liver injury.
EXPOSURE ASSESSMENT | Household Water Use and Breath Trihalomethane
Common household water-use activities, such as showering, bathing, drinking, and washing clothes or dishes, are potentially important contributors to individual exposure to trihalomethanes (THMs), the major class of chlorination disinfection by-products of water. Gordon et al. (p. 514) determined which of 12 common water-use activities resulted in the greatest THM exposures and internal doses. Showering, bathing, and machine washing of clothes and of dishes all resulted in increases in indoor-air chloroform concentrations. Only showering and bathing caused significant increases in the breath chloroform levels. Neither dibromochloromethane nor bromoform gave measurable breath concentrations.
EXPOSURE ASSESSMENT | Prevalence of Cockroach Allergen in U.S. Households
Cohn et al. (p. 522) characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations. Data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey, was used. Residents of 831 U.S. homes participated in the survey. Elevated concentrations were primarily observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. This allergen is prevalent in many settings at levels that may contribute to allergic sensitization and asthma morbidity. Likelihood of exposure can be assessed by evaluating demographic and household determinants.
TOXICOLOGY | Methylarsonous Acid Transport by Aquaglyceroporin
Many mammals methylate trivalent inorganic arsenic in the liver to species that are released into the bloodstream and excreted in urine and feces. One initial product of As(III) methylation is methylarsonous acid [MAs(III)], which is more toxic than inorganic As(III). Aquaglyceroporin (AQP) channels conduct As(III) as arsenic trioxide, the protonated form of arsenite. Liu et al. (p. 527) investigated how methylated arsenicals pass through cell membranes. The results indicate that AQPs differ both in selectivity and in transport rates of trivalent arsenicals. Identification of MAs(III) as an AQP9 substrate is an important step in understanding physiologic responses to As in mammals, including humans.
EXPOSURE ASSESSMENT | Ozone and Mortality: Exposure Response and Regulations
Time-series analyses show that ozone is associated with increased risk of premature mortality, but little is known about how O3 affects health at low concentrations. Bell et al. (p. 532) developed and applied several statistical models to data on air pollution, weather, and mortality to estimate the exposure-response curve for tropospheric O3 and risk of mortality and to evaluate whether a "safe" threshold level exists. The findings indicate that even low levels of tropospheric O3 are associated with increased risk of premature mortality. Interventions to further reduce O3 pollution would benefit public health, even in regions that meet current regulatory standards and guidelines.
Also see Science Selections, p. A240
TOXICOLOGY | Survival-Adjusted Quantal-Response Test
In rodent cancer bioassays, animals are exposed to chemical doses and followed for tumor occurrence; the tumor rates are analyzed using a survival-adjusted Cochran-Armitage (CA) trend test. An alternative survival-adjusted test procedure based on isotonic regression methodology has also been proposed. Peddada and Kissling (p. 537) introduce a new survival-adjusted test procedure that makes use of both trend tests. The new procedure competes well with the survival-adjusted CA trend test when observed tumor rates are linear in dose, and it performs substantially better when observed tumor rates are nonlinear in dose. Further, the proposed trend test almost always has a smaller false-positive rate than does the survival-adjusted CA trend test.
BIOMONITORS | Biomonitoring Chromium in Exhaled Breath Condensate
Chromium is corrosive, cytotoxic, and carcinogenic in humans and can induce acute and chronic lung tissue toxicity. Caglieri et al. (p. 542) investigated Cr levels in exhaled breath condensate (EBC) of workers exposed to Cr(VI) and assessed their relationship with biochemical changes in the airways by analyzing two EBC biomarkers of oxidative stress, hydrogen peroxide and malondialdehyde. The results demonstrate that EBC is a suitable matrix that can be used to investigate both Cr levels and biomarkers of free radical production by sampling the epithelial lining fluid of workers exposed to Cr(VI).
ENVIRONMENTAL TOXICOLOGY | Evolutionary Toxicology of the Azerbaijan Marsh Frog
Matson et al. (p. 547) used molecular methods and population genetic analyses to study the effects of chronic contaminant exposure in marsh frogs from Sumgayit, Azerbaijan. Frogs inhabiting these wetlands are exposed to complex mixtures of contaminants, including petroleum products, pesticides, heavy metals, and other industrial chemicals. Based on mitochondrial DNA control region sequence data, this region has reduced levels of genetic diversity and acts as an ecological sink, with levels of gene flow into the region exceeding gene flow out of the region. The results provide an integrated method for assessing the cumulative population impacts of chronic contaminant exposure by studying both population genetic and evolutionary effects.
CELL CYCLE CONTROL | Ionizing Radiation Synchronizes Human Fibroblasts to G0
Zhou et al. (p. 553) quantified cell cycle arrest and transcriptional responses to DNA damage induced by ionizing radiation (IR) in telomerase-expressing human diploid fibroblasts. Using the microarray analysis algorithm EPIG, the authors identified nine IR-responsive patterns of gene expression that were common to three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Cluster and principal component analyses revealed a 24-hr post-IR profile with similarity to that of G0 growth quiescence. The results indicate a highly stereotypic pattern of response to IR that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1.
CARDIOVASCULAR DISEASE | PM and Heart Rate Variability
Associations between concentrations of ambient PM2.5 (fine particulate matter < 2.5 µm aerodynamic diameter) and heart rate variability (HRV) differ by study population. Wheeler et al. (p. 560) examined the effects of ambient pollution on HRV for individuals with chronic obstructive pulmonary disease and those with recent myocardial infarction living in Atlanta, Georgia. HRV, baseline pulmonary function, and medication data were collected for each participant on 7 consecutive days in fall and/or spring. Results indicate heterogeneity in the autonomic response to air pollution due to differences in baseline health, with significant associations for ambient nitrogen dioxide, and suggest an important role for traffic-related pollution.
EPIGENETICS | Maternal Genistein Alters the Fetal Epigenome
Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Maternal dietary genistein supplementation of mice during gestation, at levels comparable with humans consuming high-soy diets, shifted the coat color of heterozygous viable yellow agouti (Avy/a) offspring toward pseudoagouti. Dolinoy et al.(p. 567) provide the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome.
Also see Science Selections, p. A240
TOXICOGENOMICS | Review of Genomic Data in Mock Submissions
The Food and Drug Administration (FDA) and the pharmaceutical industry recognize the importance of pharmacogenomics and toxicogenomics in drug development. To resolve the uncertainties surrounding the use of microarray technology and the presentation of genomic data for regulatory purposes, pharmaceutical companies and genomic technology providers have provided the FDA with reports of genomic studies that included supporting toxicology data. Leighton et al. (p. 573) describe these submissions and the assessment of data content, format, and quality control that were useful for evaluating nonclinical genomic submissions in relation to the proposed MIAME/MINTox (minimum information about a microarray experiment/minimum information needed for a toxicology experiment) recommendations.
Children's Health
CARDIOVASCULAR | Lead and Blood Pressure in Children
Because studies in children suggest a weak association between blood lead concentration and blood pressure, Chen et al. (p. 579) tested the strength of this association in children with elevated blood lead concentrations and examined whether succimer chelation changed blood pressure as it did blood lead. Systolic and diastolic blood pressures were measured in a randomized clinical trial of 780 children. Overall, there was no association between blood lead and blood pressure in these children nor did chelation with succimer change blood pressure.
Also see Science Selections, p. A241
HUMAN TOXICOLOGY | Renal and Neurologic Effects of Toxic Metals in Children
Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. de Burbure et al. (p. 584) studied the effects of these metals on the renal and dopaminergic systems in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid. Heavy metals polluting the environment can cause subtle effects on children's renal and dopaminergic systems without clear evidence of a threshold.
ENVIRONMENTAL JUSTICE | Race, Poverty, and Potential CAFO Exposures
Airborne effluent from swine confined animal feeding operations (CAFOs) may affect the health and quality of life of adults and the prevalence of asthma symptoms among children. Mirabelli et al. (p. 591) assessed the proximity of schools to the nearest CAFO and identified schools with noticeable livestock odor. Publicly available information describing the enrollment of each school was used to assess the association between race and socioeconomic status and CAFO exposure. Analyses indicate that the potential for in-school exposure to pollution arising from CAFOs and the environmental health risks associated with such exposures vary according to the racial and economic characteristics of enrolled students.
Also see Science Selections, p. A241
FETAL DEVELOPMENT | Prenatal Organochlorine Pesticide Exposure and Fetal Growth
Organochlorine (OC) pesticides were widely used as insecticides in the United States from 1940 through the 1970s. Although substantial evidence exists for the fetal toxicity of OC pesticides in animals, information on human reproductive effects is conflicting. Fenster et al. (p. 597) investigated whether the length of gestation, birth weight, and crown-heel length of infants were associated with maternal serum levels of 11 OC pesticides. With the exception of hexachlorobenzene (HCB), reductions in gestational duration were not associated with the OC pesticides. Given this population's relatively low rate of preterm delivery, the decreased length of gestation related to HCB does not seem to have had clinical implications.
EXPOSURE ASSESSMENT | 1-Hydroxypyrene in Ukrainian Children
Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure. Mucha et al. (p. 603) measured urinary 1-OHP in 48 3-year-old children who lived near a steel mill and coking facility in Mariupol, Ukraine, and compared these with 1-OHP concentrations measured in 42 children of the same age living in the capital city of Kiev. The samples from children in Mariupol have the highest reported mean urinary 1-OHP concentrations, regardless of sex, in children studied to date. This is most likely due to their proximity to a large industrial point source of PAHs.
RESPIRATORY DISEASE | Endotoxin and Respiratory Illness
Dales et al. (p. 610) carried out a longitudinal follow-up study of children born in Prince Edward Island, Canada, beginning at birth, to determine the influence of endotoxin on the incidence of acute respiratory illness during the first 2 years of life. Five-day averaged air endotoxin was measured in the homes of children, and their parents provided information by daily symptom diaries and twice-monthly telephone contact for up to 2 years. A doubling of the air endotoxin concentration was associated with an increase of 0.32 illness episodes per year adjusted for age, year of study, breast-feeding, environmental tobacco smoke exposure, child care attendance, indoor temperature, and income. Indoor mold surface area and fungal ergosterol were not significantly associated with endotoxin.
Mini-Monograph
ASTHMA | Asthma Induction and Environment: Knowns and Unknowns
Asthma incidence has increased dramatically in the United States and in other countries as a result of ill-defined changes in living conditions. The Mini-Monograph (p. 615, 620, 627, and 634) provides an overview of the U.S. Environmental Protection Agency and National Institute of Environmental Health Sciences cosponsored workshop "Environmental Influences on the Induction and Incidence of Asthma," which reviewed current scientific evidence concerning factors that may contribute to the induction of asthma. Allergen response influenced by the innate immune system, viruses, and bacterial products are important risk factors.Other factors include increased awareness of the disease, lifestyle, and activity patterns and changes in environmental exposures, and susceptibility factors. Participants developed a framework for research hypotheses regarding the effects of environmental exposures on asthma incidence and induction.