Response of the East Antarctic Ice Sheet to past and future climate change.

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied.

Polycomb-group recruitment to a Drosophila target gene is the default state that is inhibited by a transcriptional activator.

Polycomb-group (PcG) proteins are epigenetic regulators that maintain the transcriptional repression of target genes following their initial repression by transcription factors. PcG target genes are repressed in some cells, but active in others. Therefore, a mechanism must exist by which PcG proteins distinguish between the repressed and active states and only assemble repressive chromatin environments at target genes that are repressed. Here, we present experimental evidence that the repressed state of a Drosophila PcG target gene, giant (gt), is not identified by the presence of a repressor. Rather, de novo establishment of PcG-mediated silencing at gt is the default state that is prevented by the presence of an activator or coactivator, which may inhibit the catalytic activity of Polycomb-repressive complex 2 (PRC2).

Evaluation of Antibacterial and Cytotoxicity Properties of Silver Nanowires and Their Composites with Carbon Nanotubes for Biomedical Applications.

In this work, we prepared silver nanowires (AgNWs) via the polyol method in the presence or absence of single wall carbon nanotubes (CNTs) and tested their physicochemical, antibacterial and cytotoxic properties. Results showed that the introduction of CNTs lead to the formation of AgNWs at lower temperature, but the final product characteristics of AgNWs and AgNWs-CNT were not significantly different. AgNWs exhibited antibacterial properties against all the studied bacterial species via the formation of oxygen reactive species (ROS) and membrane damage. Furthermore, AgNWs exhibited a dose-dependent and time-dependent toxicity at concentrations ≥ 10 µg/mL. Fibroblasts appeared to be more resistant than human colorectal adenocarcinoma (Caco-2) and osteoblasts to the toxicity of AgNWs. The cytotoxicity of AgNWs was found to be related to the formation of ROS, but not to membrane damage. Overall, these results suggest that AgNWs are potential antibacterial agents against E. coli, S. aureus, MRSA and S. saprophyticus, but their dosage needs to be adjusted according to the route of administration.

Differential Contributions of DNA-Binding Proteins to Polycomb Response Element Activity at the Drosophila giant Gene.

Polycomb-group (PcG) proteins are evolutionarily conserved epigenetic regulators whose primary function is to maintain the transcriptional repression of target genes. Recruitment of Drosophila melanogaster PcG proteins to target genes requires the presence of one or more Polycomb Response Elements (PREs). The functions or necessity for more than one PRE at a gene are not clear and individual PREs at some loci may have distinct regulatory roles. Various combinations of sequence-specific DNA-binding proteins are present at a given PRE, but only Pleiohomeotic (Pho) is present at all strong PREs. The giant (gt) locus has two PREs, a proximal PRE1 and a distal PRE2. During early embryonic development, Pho binds to PRE1 ∼30-min prior to stable binding to PRE2. This observation indicated a possible dependence of PRE2 on PRE1 for PcG recruitment; however, we find here that PRE2 recruits PcG proteins and maintains transcriptional repression independently of Pho binding to PRE1. Pho-like (Phol) is partially redundant with Pho during larval development and binds to the same DNA sequences in vitro Although binding of Pho to PRE1 is dependent on the presence of consensus Pho-Phol-binding sites, Phol binding is less so and appears to play a minimal role in recruiting other PcG proteins to gt Another PRE-binding protein, Sp1/Kruppel-like factor, is dependent on the presence of Pho for PRE1 binding. Further, we show that, in addition to silencing gene expression, PcG proteins dampen transcription of an active gene.

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

Polybrominated Diphenyl Ethers and Biphenyl in Serum: Time Trend Study from the National Health and Nutrition Examination Survey for Years 2005/06 through 2013/14.

Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and ≥60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and ≥60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and ≥60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.

What Is the Role of Elective Neck Dissection in the Management of Patients With Buccal Squamous Cell Carcinoma and Clinically Negative Neck?

PURPOSE: Buccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to spread exist and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in patients with clinically negative neck (N0) is not clear. This study aims to answer the following research question: Among patients with N0 BSCC, does END improve locoregional control rates, distant metastasis rates, and 2- and 5-year survival rates? MATERIALS AND METHODS: A retrospective cohort study was conducted. The sample included patients who received a diagnosis of BSCC. The primary predictor variable was END status (yes or no). Five institutions participated between June 2001 and June 2011: University of Washington, University of Michigan, University of Tennessee, North Memorial Oral and Maxillofacial Surgery in Minnesota, and Head and Neck Surgical Associates (Portland, OR). The primary outcome variable was locoregional recurrence. Secondary outcome variables were distant metastasis and 2- and 5-year survival rates. Other variables collected were demographic characteristics, initial operation, adjuvant therapy, clinical and pathologic data, and staging. Kaplan-Meier and Cox proportional hazards statistics were computed. RESULTS: The sample was composed of 98 patients with clinical N0 BSCC. The mean age was 66 years (range, 30-88 years), and 54% were men. Of the patients, 74 (76%) underwent END. The locoregional recurrence-free rate was 61% for END versus 38% for no END (P = .042). The distant metastasis rate was 4% for END versus 9% for no END. The 2- and 5-year disease-free survival rates were 91% and 75% (P = .042), respectively, for END and 85% and 63% (P = .019), respectively, for no END. CONCLUSIONS: END had a therapeutic effect, as evidenced by a lower locoregional recurrence rate, lower distant metastasis rate, and improved 2- and 5-year survival rates.

De novo recruitment of Polycomb-group proteins in Drosophila embryos.

Polycomb-group (PcG)-mediated transcriptional repression of target genes can be delineated into two phases. First, following initial repression of target genes by gene-specific transcription factors, PcG proteins recognize the repressed state and assume control of the genes' repression. Second, once the silenced state is established, PcG proteins may maintain repression through an indefinite number of cell cycles. Little is understood about how PcG proteins initially recognize the repressed state of target genes and the steps leading to de novo establishment of PcG-mediated repression. We describe a genetic system in which a Drosophila PcG target gene, giant (gt), is ubiquitously repressed during early embryogenesis by a maternally expressed transcription factor, and show the temporal recruitment of components of three PcG protein complexes: PhoRC, PRC1 and PRC2. We show that de novo PcG recruitment follows a temporal hierarchy in which PhoRC stably localizes at the target gene at least 1 h before stable recruitment of PRC2 and concurrent trimethylation of histone H3 at lysine 27 (H3K27me3). The presence of PRC2 and increased levels of H3K27me3 are found to precede stable binding by PRC1.

Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene in 7- and 9-Year-Old Children and Their Mothers in the Center for the Health Assessment of Mothers and Children of Salinas Cohort.

We report longitudinal serum concentrations of select persistent organic pollutants (POPs) in children at ages 7 and 9 years and in their mothers prenatally and again when the children were 9 years old. The participating families were enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income Hispanic families residing in the Salinas Valley, California. We observed decreasing concentrations in the mothers with year of serum collection (2009 vs 2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for 2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and 2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for weight gain as the children aged from 7 to 9 years, we observed an annual decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not associated with time of serum collection and instead showed an -0.9% to -2.6% decrease per kilogram of weight gain during the study period (p < 0.05). In the case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7% decrease in serum concentration per year of aging (p < 0.05), except for 2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), which were not associated with time of serum draw. 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain between the two sampling points (p < 0.001). These findings suggest that as children grow, dilution in a larger body size plays an important role in explaining reductions in body burden in the case of traditional POPs such as PCBs and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained by reduction in exposure, as illustrated by decreased concentrations in more recent years, possibly amplified by presumed shorter biological half-life than other POPs.

Polybrominated diphenyl ether serum concentrations in a Californian population of children, their parents, and older adults: an exposure assessment study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many household items. Given concerns over their potential adverse health effects, we identified predictors and evaluated temporal changes of PBDE serum concentrations. METHODS: PBDE serum concentrations were measured in young children (2-8 years old; N = 67), parents of young children (<55 years old; N = 90), and older adults (≥55 years old; N = 59) in California, with concurrent floor wipe samples collected in participants' homes in 2008-2009. We also measured serum concentrations one year later in a subset of children (N = 19) and parents (N = 42). RESULTS: PBDE serum concentrations in children were significantly higher than in adults. Floor wipe concentration is a significant predictor of serum BDE-47, 99, 100 and 154. Positive associations were observed between the intake frequency of canned meat and serum concentrations of BDE-47, 99 and 154, between canned meat entrees and BDE-154 and 209, as well as between tuna and white fish and BDE-153. The model with the floor wipe concentration and food intake frequencies explained up to 40% of the mean square prediction error of some congeners. Lower home values and renting (vs. owning) a home were associated with higher serum concentrations of BDE-47, 99 and 100. Serum concentrations measured one year apart were strongly correlated as expected (r = 0.70-0.97) with a slight decreasing trend. CONCLUSIONS: Floor wipe concentration, food intake frequency, and housing characteristics can explain 12-40% of the prediction error of PBDE serum concentrations. Decreasing temporal trends should be considered when characterizing long-term exposure.

Polybrominated Diphenyl Ethers and Other Persistent Organic Pollutants in Serum Pools from the National Health and Nutrition Examination Survey: 2001-2002.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in serum pools from participants 3-5, 6-11, 12-19, 20-39, 40-59, and ≥60 years of age from the 2001-2002 National Health and Nutrition Examination Survey. For 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47), the unweighted (not adjusted for sampling weights) arithmetic mean concentration (±95% confidence interval) was 3.4 times higher in 3-5-year-olds (216 ± 30 ng/g of lipid) than in 12-19-year-olds (64 ± 11 ng/g of lipid), with no apparent change with increasing age for adults ≥20 years of age. By contrast, unweighted arithmetic mean concentrations of traditional persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and 2,2',3,3',4,4',5,5'-octachlorobiphenyl (PCB194) were 2- and 20-fold higher, respectively, in persons ≥60 years than in 12-19-year-old adolescents. Findings suggest higher exposures to PBDEs but lower exposures to traditional POPs in 3-5-year-old children than in adults.

Polybrominated diphenyl ethers, polychlorinated biphenyls, and persistent pesticides in serum from the national health and nutrition examination survey: 2003-2008.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in pooled samples representative of the general noninstitutionalized population of the United States. The pools were made from individual sera from the National Health and Nutrition Examination Survey (NHANES) during 2005/06 and 2007/08. The pooled concentrations have been contrasted to NHANES 2003/04 individual measurements to evaluate changes in concentration over time and within survey period differences among age groups, race/ethnicity groups (Mexican American, non-Hispanic Black, non-Hispanic White), and sex. The arithmetic mean serum concentrations of several PCB congeners decreased from NHANES 2003/04 through 2007/08. Larger percentage reductions were seen for younger subjects (12-19 years) compared with older subjects (≥60 years). For example, the arithmetic mean concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) was 36% lower in 12-19 year old adolescents when comparing NHANES 2007/08 with 2003/04; while for subjects over the age of 60 a 14% lower concentration was seen, although, the 95% confidence intervals overlapped. Similarly, the arithmetic mean serum concentrations of tri- to hexaBDEs were lower in NHANES 2007/08 than in 2003/04; however, most confidence intervals of the arithmetic means overlapped. These findings suggest that a reduction in PBDE serum concentrations cannot yet be detected following the discontinuation of pentaBDE in 2004.

Mapping polycomb response elements at the Drosophilla melanogaster giant locus.

Polycomb-group (PcG) proteins are highly conserved epigenetic transcriptional regulators. They are capable of either maintaining the transcriptional silence of target genes through many cell cycles or enabling a dynamic regulation of gene expression in stem cells. In Drosophila melanogaster, recruitment of PcG proteins to targets requires the presence of at least one polycomb response element (PRE). Although the sequence requirements for PREs are not well-defined, the presence of Pho, a PRE-binding PcG protein, is a very good PRE indicator. In this study, we identify two PRE-containing regions at the PcG target gene, giant, one at the promoter, and another approximately 6 kb upstream. PRE-containing fragments, which coincide with localized presence of Pho in chromatin immunoprecipitations, were shown to maintain restricted expression of a lacZ reporter gene in embryos and to cause pairing-sensitive silencing of the mini-white gene in eyes. Our results also reinforce previous observations that although PRE maintenance and pairing-sensitive silencing activities are closely linked, the sequence requirements for these functions are not identical.

Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants historically used in textiles, furniture, and electronic products. Recent studies have documented widespread PBDE exposure to humans, with higher levels measured in children than adults. We analyzed 10 tri- to hepta-BDE congener levels in blood collected from 7-year old Mexican-American children living in an agriculture community in California (n = 272). The most frequently detected PBDE congeners in child serum were BDE-47, -99, -100, and -153, all of which were measured in >99% of the children. We used multiple linear regression models to examine associations between child total PBDE levels (ng/g lipid) and determinants of exposure. Factors positively associated with higher PBDE levels in the children were total PBDE levels in maternal serum during pregnancy, duration of exclusive breastfeeding, and having no safe places to play in their neighborhood. Child BMI was inversely associated with serum PBDE levels (regression p-values <0.05). Our findings confirm that exposure to the penta-BDE mixture is ongoing, and that Mexican-American children living in California may be experiencing higher PBDE exposure from their environment compared to children sampled from the general U.S. population. Additional research is needed to assess the health impacts of these exposures.

Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort.

We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ≥3 pieces of stuffed furniture in their homes (p < 0.05). Women's total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ≥3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in women's serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.

Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes.

BACKGROUND: There is emerging evidence that background exposure to persistent organic pollutants (POPs) are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study. METHODOLOGY/PRINCIPAL FINDINGS: The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR) were study outcomes at 2005-06 (year 20). The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves. CONCLUSIONS/SIGNIFICANCE: Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism.

A method for rapid, non-targeted screening for environmental contaminants in household dust.

Household dust can be a major source of human exposure to environmental contaminants such as polybrominated diphenyl ethers, pesticides, and other compounds. This work shows a screening technique that may be used to identify components in an environmental sample as xenobiotics based on mass spectral characteristics of classes of compounds that may be expected to be present in the environment. Household dust (SRM-2585) from the National Institute of Standards and Technology (NIST) was extracted with hexane using accelerated solvent extraction. Large molecules, such as triglycerides and fatty acids were removed with gel permeation chromatography. The extract was then concentrated and analyzed by comprehensive two dimensional gas chromatography coupled to a time of flight mass spectrometer. The resulting peak table was automatically filtered to identify compound classes such as phthalates, polycyclic aromatic hydrocarbons and their heterocyclic analogs, chlorinated compounds, brominated compounds, and nitro compounds. While phthalates can be identified by abundances at specific masses, the identification of the remaining classes is based on the identification of the molecular ion and identification of isotope clusters or other spectral characteristics. The technique detected compounds identified and quantified by NIST as well as compounds not identified by NIST in the sample. By comparison with concentrations determined by NIST for the analytes found, the technique is able to identify analytes in these compound classes at concentrations as low as 10-20 ng/g dust.

Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case-control study.

BACKGROUND: Low doses of some persistent organic pollutants (POPs) associate cross-sectionally with type 2 diabetes, whereas associations with high POP exposures are inconsistent. OBJECTIVES: We investigated whether several POPs prospectively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. METHODS: Participants in this nested case-control study were diabetes free in 1987-1988. By 2005-2006, the 90 controls remained free of diabetes, whereas the 90 cases developed diabetes. Using serum collected in 1987-1988, we measured 8 organochlorine pesticides, 22 polychlorinated biphenyl congeners (PCBs), and 1 polybrominated biphenyl (PBB). We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey (NHANES) in 2003-2004. We computed odds ratios (ORs) for incident diabetes using logistic regression analysis. RESULTS: Chlorinated POPs in CARDIA in 1987-1988 were much higher than corresponding NHANES 2003-2004 concentrations. POPs showed nonlinear associations with diabetes risk. The highest risk was observed in the second quartiles of trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB153-a finding that suggests low-dose effects. We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum. The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index > or = 30 kg/m2. CONCLUSIONS: Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity.