Boston University Superfund Research Program

On The Cover

An Indian girl uses a blowpipe to breathe more life into a cooking fire. According to the World Health Organization, about 2 billion people worldwide cook over fire.

Background: The National Children’s Study (NCS) is the most ambitious study ever attempted in the US to assess how environmental factors impact child health and development. It aims to follow 100,000 children from gestation until age 21. Success requires breaking new interdisciplinary ground, starting with how to select the sample of over 1000 children in each of 105 study sites; no standardized protocol exists for stratification of the target population by factoring in the diverse environments it inhabits. Worcester County, like other sites, stratifies according to local conditions and local knowledge, subject to probability sampling rules.

Objectives: We answer: How do we divide Worcester County into viable strata that represent its health-relevant environmental and socio-demographic heterogeneity, subject to sampling rules? What potential does our approach have to inform stratification at other sites?

Results: We developed a multivariable vulnerability based method for spatial sampling, consisting of two descriptive indices: a hazards/stressors exposure index (comprising three proxy variables); and an adaptive capacity/socio-demographic character index (five variables). Multivariable, health-relevant stratification up-front may improve detection power for environment-child health associations down the line. Eighteen strata capture countywide heterogeneity in the indices, and have optimal relative homogeneity within each. They achieve comparable expected birth counts and conform to local concepts of space.

Conclusion: The approach offers moderate-high potential to inform other sites, limited by inter-site differences in data availability, geo-demographics and technical capacity. Energetic community engagement from the start promotes local stratification coherence, plus vital researcher-community trust and co-ownership for sustainability.

Background: Black carbon is a marker of traffic pollution which has been associated with blood pressure (BP), although findings have been inconsistent. MicroRNAs are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of microRNAs to maturity influence susceptibility to black carbon has not been elucidated.

Objectives: We investigated the association between black carbon and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in microRNA processing genes.

Methods: Repeated measures analyses were performed using data from Normative Aging Study. Complete covariate data were available for 789 participants with 1-6 study visits between 1995 and 2008. In models of systolic and diastolic BP we examined SNP-by-black carbon interactions with 19 microRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle and meteorological factors.

Results: A 1 standard deviation increase in black carbon (0.415 µg/m³) was associated with 3.04 mmHg higher systolic (95% Confidence Interval (CI): 2.29, 3.79) and 2.28 mmHg higher diastolic BP (95% CI: 1.88, 2.67). Interactions modifying black carbon associations were observed with SNPs in the DICER, GEMIN4, and DGCR8 genes, and in GEMIN3 and GEMIN4 predicting diastolic and systolic BP respectively.

Conclusions: We observed evidence of effect modification of the association between BP and 7-day black carbon moving averages by SNPs associated with miRNA processing. While the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing black carbon effects.

The Brownfield Inventory Tool (BIT) is a Free, web-based, comprehensive brownfields program management tool. Cities, regional coalitions, and tribes can use BIT to create site inventories; submit reports such as the multiple property profile form (in excel); generate maps; and log administrative information about brownfields and other environmental programs. This CLU-IN session will provide a live demonstration of how to use BIT. Briefing slides with screenshots will also be available for those without internet access during the CLU-IN session.

BIT is available at http://tab-bit.org. Please click on "Register" to create your password for access to site inventory tools and all other features on the web page. For subsequent visits, use the Login link to enter your e-mail and password.

The governments leading toxicologists and environmental health scientists will share their latest scientific accomplishments, offer continuing education courses, discuss funding and training opportunities, receive input on future research priorities, and more, at the Society of Toxicology (SOT) annual meeting. Staff from the National Institute of Environmental Health Sciences (NIEHS), one of the National Institutes of Health, and the National Toxicology Program (NTP) will speak at more than 30 different sessions and present 60 posters on topics ranging from improving toxicity testing to translational research. Many NIEHS grantees will also showcase their research. For the first time this year, live updates will be provided by conference participants on the NIEHS and NTP web sites. "If you are interested in knowing what researchers and toxicologists in government, academia and industry are doing to advance the pace of biomedical research and safeguard the public's health, the SOT meeting is the place to be," said NIEHS/NTP Director Linda Birnbaum, Ph.D. "For toxicologists, this is our Olympics." The SOT Annual Meeting is the largest toxicology meeting and exhibition in the world, attracting approximately 6,500 scientists from industry, academia, and government. When: March 7-11, 2010. Society of Toxicology Annual Meeting - All events will be held at the Salt Palace Convention Center in Salt Lake City, Utah. For more information about the SOT annual meeting, visit http://www.toxicology.org/AI/MEET/AM2010/

Background: Inactivation of p53 is involved in arsenite-induced tumorigenesis; the molecular mechanisms, however, remain poorly understood.

Objective: To investigate the molecular mechanisms underlying the inactivation of p53 and neoplastic transformation of human embryo lung fibroblast (HELF) cells induced by arsenite.

Methods: Anchorage-independent growth assays were performed, and tumorigenicity in intact animals was assessed to confirm arsenite-induced neoplastic transformation. The levels and functions of p53, NF-κB (a key transcriptional regulator), and mot-2 (a p53 inhibitor) and their relationships in arsenite-induced transformed HELF cells were determined by 2-DE, RT-PCR, Western blot, immunofluorescence, and co-immunoprecipitation assays.

Results: Exposure of HELF cells to low levels of arsenite increased their proliferation rate and anchorage-independent growth, and disrupted normal contact inhibition. When introduced into nude mice, transformed cells were tumorigenic. Proteomic analysis was used to identify proteins with altered expression between untreated and arsenite-exposed cells. There was decreased expression of NKRF (an inhibitor of NF-κB-mediated gene transcription), increased expression of mot-2, and increased activation of NF-κB. Changes in cells exposed to 1.0 μM arsenite were more marked than changes in cells exposed to 0.5 or 2.0 μM arsenite. Inactivation of NF-κB prevented malignant transformation induced by 1.0 μM arsenite. Moreover, a mechanism was identified whereby NF-κB regulated p53. Specifically, activation of NF-κB up-regulated mot-2 expression, which preventsed nuclear translocation of p53 and switched the binding preference of the p53 and NF-κB co-activator CBP from p53 to NF-κB.

Conclusions: Mot-2-mediated crosstalk between NF-κB and p53 appears to be involved in arsenite-induced tumorigenesis of HELF cells.

The CLU-IN Upcoming Courses and Conferences section was updated on March 2, 2010. There are 5 new entries, for a total of 129 upcoming courses and conferences related to hazardous waste remediation:

• Analyzing Risk: Science, Assessment and Management, Mar 16 , 2010, Boston, MA
• Risk Assessment and Risk Management: Determination and Application of Risk-Based Values, Apr 8 , 2010, INTERNET
• Symposium on the Application of Geophysics to Environmental and Engineering Problems (SAGEEP), Apr 11 - 15, 2010, Keystone, CO
• Quality Considerations for Munitions Response Projects, Apr 13 , 2010, INTERNET
• Use of Risk Assessment in Management of Contaminated Sites, Apr 27 , 2010, INTERNET

Background: Emerging evidence suggests that the systemic vasculature may be a target of inhaled pollutants of vehicular origin. We have identified several murine markers of vascular toxicity that appear sensitive to inhalation exposures to combustion emissions.

Objectives: We sought to examine the relative impact of various pollutant atmospheres and specific individual components on these markers of altered vascular transcription and lipid peroxidation.

Methods: Apolipoprotein E knockout (ApoE^-/-) mice were exposed to whole combustion emissions (gasoline, diesel, coal, hardwood), biogenically-derived secondary organic aerosols (SOA), or prominent combustion-source gases (nitric oxide, nitrogen dioxide, carbon monoxide) for 6 h/d x 7 days. Aortas were assayed for transcriptional alterations of endothelin-1 (ET-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), and heme oxygenase-1 (HO-1), along with measures of vascular lipid peroxides (LPO) and gelatinase activity.

Results: Transcriptional alterations were noted with exposures to gasoline and diesel emissions. Interestingly, ET-1 and MMP-9 transcriptional effects could be recreated by exposure to carbon monoxide and nitric oxide, but not nitrogen dioxide or SOA. Gelatinase activity aligned with levels of volatile hydrocarbons and also monoxide gases. Neither gases nor particles were able to induce vascular LPO despite potent effects from whole vehicular emissions.

Conclusions: In this head-to-head comparison of the effects of several pollutants and pollutant mixtures, we found an important contribution to vascular toxicity from readily bioavailable monoxide gases and possibly from volatile hydrocarbons. These data support a role for traffic-related pollutants in driving cardiopulmonary morbidity and mortality.

University of Arizona Superfund Research Program (SRP) has been asked to serve as the "go to" experts for educating the public about a recent set of dust emission violations by the ASARCO Mission Complex Mine Tailings.

Rep. Edward Markey (D-MA) is calling on the EPA to consider more stringent regulations on triclosan (TCS) and triclocarbon (TCC), antimicrobial ingredients found in myriad personal care and cleaning products.