Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study

Abstract Background Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely. Methods A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry. Results BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 μg/L to 6.7 μg/L; uncorrected geometric mean was 1.52 μg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05). Conclusions This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.http://deepblue.lib.umich.edu/bitstream/2027.42/78251/1/1476-069X-9-62.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78251/2/1476-069X-9-62.pdfPeer Reviewe

Comparing United States and Canadian population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study

The Centers for Disease Control and Prevention provides biomonitoring data in the United States as part of the National Health and Nutrition Examination Survey (NHANES). Recently, Statistics Canada initiated a similar survey — the Canadian Health Measures Survey (CHMS). Comparison of US and Canadian biomonitoring data can generate hypotheses regarding human exposures from environmental media and consumer products. To ensure that such comparisons are scientifically meaningful, it is essential to first evaluate aspects of the surveys' methods that can impact comparability of data. We examined CHMS and NHANES methodologies, using bisphenol A (BPA) as a case study, to evaluate whether survey differences exist that would hinder our ability to compare chemical concentrations between countries. We explored methods associated with participant selection, urine sampling, and analytical methods. BPA intakes were also estimated to address body weight differences between countries. Differences in survey methods were identified but are unlikely to have substantial impacts on inter-survey comparisons of BPA intakes. BPA intakes for both countries are below health-based guidance values set by the US, Canada and the European Food Safety Authority. We recommend that before comparing biomonitoring data between surveys, a thorough review of methodologic aspects that might impact biomonitoring results be conducted

Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study

Abstract Background Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. Methods We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Results Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Conclusions Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.http://deepblue.lib.umich.edu/bitstream/2027.42/112495/1/12940_2011_Article_523.pd

Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006

<p>Abstract</p> <p>Background</p> <p>Bisphenol A (BPA) and polyfluoroalkyl chemicals (PFCs) are suspected endocrine disrupting compounds known to be ubiquitous in people's bodies. Population disparities in exposure to these chemicals have not been fully characterized.</p> <p>Methods</p> <p>We analyzed data from the 2003-2006 National Health and Nutrition Examination Survey. Using multivariable linear regression we examined the association between urinary concentrations of BPA, serum concentrations of four PFCs, and multiple measures of socioeconomic position (SEP): family income, education, occupation, and food security. We also examined associations with race/ethnicity.</p> <p>Results</p> <p>All four PFCs were positively associated with family income, whereas BPA was inversely associated with family income. BPA concentrations were higher in people who reported very low food security and received emergency food assistance than in those who did not. This association was particularly strong in children: 6-11 year-olds whose families received emergency food had BPA levels 54% higher (95% CI, 13 to 112%) than children of families who did not. For BPA and PFCs we saw smaller and less consistent associations with education and occupation. Mexican Americans had the lowest concentrations of any racial/ethnic group of both types of chemicals; for PFCs, Mexican Americans not born in the U.S. had much lower levels than those born in the U.S.</p> <p>Conclusions</p> <p>People with lower incomes had higher body burdens of BPA; the reverse was true for PFCs. Family income with adjustment for family size was the strongest predictor of chemical concentrations among the different measures of SEP we studied. Income, education, occupation, and food security appear to capture different aspects of SEP that may be related to exposure to BPA and PFCs and are not necessarily interchangeable as measures of SEP in environmental epidemiology studies. Differences by race/ethnicity were independent of SEP.</p

Chronic oxidative stress increases growth and tumorigenic potential of MCF-7 breast cancer cells.

Accumulating evidence suggests that exposures to elevated levels of either endogenous estrogen or environmental estrogenic chemicals are associated with breast cancer development and progression. These natural or synthetic estrogens are known to produce reactive oxygen species (ROS) and increased ROS has been implicated in both cellular apoptosis and carcinogenesis. Though there are several studies on direct involvement of ROS in cellular apoptosis using short-term exposure model, there is no experimental evidence to directly implicate chronic exposure to ROS in increased growth and tumorigenicity of breast cancer cells. Therefore, the objective of this study was to evaluate the effects of chronic oxidative stress on growth, survival and tumorigenic potential of MCF-7 breast cancer cells. MCF-7 cells were exposed to exogenous hydrogen peroxide (H2O2) as a source of ROS at doses of 25 µM and 250 µM for acute (24 hours) and chronic period (3 months) and their effects on cell growth/survival and tumorigenic potential were evaluated. The results of cell count, MTT and cell cycle analysis showed that while acute exposure inhibits the growth of MCF-7 cells in a dose-dependent manner, the chronic exposure to H2O2-induced ROS leads to increased cell growth and survival of MCF-7 cells. This was further confirmed by gene expression analysis of cell cycle and cell survival related genes. Significant increase in number of soft agar colonies, up-regulation of pro-metastatic genes VEGF, WNT1 and CD44, whereas down-regulation of anti-metastatic gene E-Cadherin in H2O2 treated MCF-7 cells observed in this study further suggests that persistent exposure to oxidative stress increases tumorigenic and metastatic potential of MCF-7 cells. Since many chemotherapeutic drugs are known to induce their cytotoxicity by increasing ROS levels, the results of this study are also highly significant in understanding the mechanism for adaptation to ROS-induced toxicity leading to acquired chemotherapeutic resistance in breast cancer cells

Histogram showing the effect of chronic exposure to H₂O₂ in MCF-7 on colony counts in soft agar assay.

<p>Colony numbers were converted into percentage of control (control = 100%). The error bars represent the standard error of the mean (±SEM). Statistically significant changes (p<0.05) when compared to untreated control are indicated by symbol *.</p

Chronic oxidative stress increases resistance to doxorubicin-induced cytotoxicity in renal carcinoma cells potentially through epigenetic mechanism. Mol Pharmacol 89:27–41.

ABSTRACT Renal cell carcinoma is the most common form of kidney cancer and is highly resistant to chemotherapy. Although the role of oxidative stress in kidney cancer is known, the chemotherapeutic response of cancer cells adapted to chronic oxidative stress is not clear. Hence, the effect of oxidative stress on sensitivity to doxorubicin-induced cytotoxicity was evaluated using an in vitro model of human kidney cancer cells adapted to chronic oxidative stress. Results of MTT-and anchorage-independent growth assays and cell cycle analysis revealed significant decrease in sensitivity to doxorubicin in Caki-1 cells adapted to oxidative stress. Changes in the expression of genes involved in drug transport, cell survival, and DNA repair-dependent apoptosis further confirmed increased resistance to doxorubicin-induced cytotoxicity in these cells. Decreased expression of mismatch repair (MMR) gene MSH2 in cells exposed to oxidative stress suggests that loss of MMR-dependent apoptosis could be a potential mechanism for increased resistance to doxorubicin-induced cytotoxicity. Additionally, downregulation of HDAC1, an increase in the level of histone H3 acetylation, and hypermethylation of MSH2 promoter were also observed in Caki-1 cells adapted to chronic oxidative stress. DNA-demethylating agent 5-Aza-2dC significantly restored the expression of MSH2 and doxorubicin-induced cytotoxicity in Caki-1 cells adapted to chronic oxidative stress, suggesting the role of DNA hypermethylation in inactivation of MSH2 expression and consequently MMRdependent apoptosis in these cells. In summary, this study for the first time provides direct evidence for the role of oxidative stress in chemotherapeutic resistance in renal carcinoma cells potentially through epigenetic mechanism

Real time quantitative reverse transcription PCR analysis of gene expression of cell growth and survival related genes.

<p>Total RNA isolated from MCF-7 cells with acute and chronic exposure to H₂O₂ was used to perform one step real-time quantitative reverse transcription PCR as described in materials and methods. Cycle threshold value (Ct value) of each gene was normalized to the Ct value of housekeeping gene GAPDH obtained from the same sample. The gene expression in fold change was calculated and histogram was plotted using the means of triplicate values. Results of acute (Figure 4A) and chronic (Figure 4B) exposure were presented in separate histograms. Statistically significant change (p<0.05) in gene expression in treated groups as compared to the untreated control is indicated by symbol *.</p