Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Cell cycle, apoptosis, cell differentiation, and lipid metabolism gene expression in endometriotic tissue and exposure to parabens and benzophenones.

AIM: To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs). METHODS: This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels. RESULTS: A total of 8 out 13 genes (61.5 %) were expressed in >75 % of the samples. Exposure to congeners of PBs and/or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers). CONCLUSIONS: Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.

Biomonitoring bisphenols, parabens, and benzophenones in breast milk from a human milk bank in Southern Spain.

BACKGROUND: Human breast milk is considered the optimal source of nutrition for infants. Milk from breast milk banks offers an alternative to infant formulas for vulnerable hospitalized neonates most likely to benefit from exclusive human milk feeding. However, breast milk can also be a source of exposure to environmental contaminants, including endocrine-disrupting chemicals (EDCs). AIM: To evaluate concentrations of phenolic EDCs, including bisphenols, parabens (PBs), and benzophenones (BPs), in samples from a human milk bank in Granada, Southern Spain and to explore sociodemographic, reproductive, and lifestyle factors related to their concentrations in the milk. METHODS: Concentrations of three bisphenols [bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS)], four PBs [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP)], and six BPs [BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP] were determined in milk samples from 83 donors. Information on potential explanatory variables was gathered using the milk bank donor form and an ad hoc questionnaire. Multiple linear and logistic regression models were fitted. RESULTS: Detectable concentrations were found of at least one of the analyzed compounds in all donor breast milk samples and at least five compounds in one-fifth of them. The most frequently detected compounds were MeP (90.5%), BP-3 (75.0%), EtP (51.2%), n-PrP (46.4%), and BPA (41.7%). Median concentrations ranged between <0.10 ng/mL (n-PrP, n-BuP, BP-1) and 0.59 ng/mL (BP-3). No sample contained detectable concentrations of BPF, BPS, or most BPs (BP-2, BP-6, BP-8, and 4- hydroxy-BP). Breast milk phenol concentrations were associated with parity, the utilization of deodorants, mouthwash, skin care products, and cosmetics, and the intake of nutritional supplements. CONCLUSIONS: Results reveal the widespread presence of BPA, PBs, and BP-3 in donor breast milk samples, highlighting the need for preventive measures to enhance the benefits of breast milk from milk banks and from breastfeeding women in general.

Concentrations of bisphenols, parabens, and benzophenones in human breast milk: A systematic review and meta-analysis.

BACKGROUND: Breast milk is the main source of nutrition for infants but may be responsible for their exposure to environmental chemicals, including endocrine-disrupting chemicals. AIM: To review available evidence on the presence and concentrations of bisphenols, parabens (PBs), and benzophenones (BPs) in human milk and to explore factors related to exposure levels. METHODS: A systematic review was carried out using Medline, Web of Science, and Scopus databases, conducting a comprehensive search of peer-reviewed original articles published during the period 2000-2020, including epidemiological and methodological studies. Inclusion criteria were met by 50 studies, which were compiled by calculating weighted detection frequencies and arithmetic mean concentrations of the chemicals. Their risk of bias was assessed using the ROBINS-I checklist. RESULTS: Among the 50 reviewed studies, concentrations of bisphenols were assessed by 37 (74.0%), PBs by 21 (42.0%), and BPs by 10 (20.0%). Weighted detection frequencies were 63.6% for bisphenol-A (BPA), 27.9-63.4% for PBs, and 39.5% for benzophenone-3 (BP-3). Weighted mean concentrations were 1.4 ng/mL for BPA, 0.2-14.2 ng/mL for PBs, and 24.4 ng/mL for BP-3. Mean concentrations ranged among studies from 0.1 to 3.9 ng/mL for BPA, 0.1 to 1063.6 ng/mL for PBs, and 0.5 to 72.4 ng/mL for BP-3. The highest concentrations of BPA and PBs were reported in samples from Asia (versus America and Europe). Higher BPA and lower methyl-paraben concentrations were observed in samples collected after 2010. Elevated concentrations of these chemicals were associated with socio-demographic and lifestyle factors in eight studies (16.0%). Two epidemiological studies showed moderate/serious risk of bias. CONCLUSIONS: This systematic review contributes the first overview of the widespread presence and concentrations of bisphenols, PBs, and BPs in human breast milk, revealing geographical and temporal variations. The methodological heterogeneity of published studies underscores the need for well-conducted studies to assess the magnitude of exposure to these chemicals from human milk.

Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study.

AIM: To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found. METHODS: This case-control study comprised a subsample of 124 women (35 cases; 89 controls). Endometriosis was confirmed (cases) or ruled out (controls) by laparoscopy, with visual inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Urinary concentrations of benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-hydroxibenzophenone (4-OH-BP), methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP), and biomarkers of oxidative stress [lipid peroxidation (TBARS) and total antioxidant power (TAP)] were quantified. Information was gathered on the frequency of use of cosmetics and PCPs. Associations between the frequency of cosmetics/PCP use, urinary concentrations of benzophenones and parabens, oxidative stress, and endometriosis risk were explored in logistic and linear multivariable regression analyses. RESULTS: The frequency of utilization of certain cosmetics and PCPs was significantly associated with urinary concentrations of benzophenones and parabens. After adjustment for potential confounders, the risk of endometriosis was increased in women in the second versus first terciles of MeP (OR = 5.63; p-value<0.001), BP-1 (OR = 5.12; p-value = 0.011), BP-3 (OR = 4.98; p-value = 0.008), and Æ©BPs (OR = 3.34; p-value = 0.032). A close-to-significant relationship was observed between TBARS concentrations and increased endometriosis risk (OR = 1.60, p-value = 0.070) and an inverse association between TAP concentrations and this risk (OR = 0.15; p-value = 0.048). Oxidative stress results did not modify associations observed between benzophenone/paraben exposure and endometriosis risk. CONCLUSIONS: Our findings indicate that the frequency of cosmetics and PCP utilization is a strong predictor of exposure to certain benzophenone and paraben congeners. These compounds may increase the risk of endometriosis in an oxidative stress-independent manner. Further studies are warranted to corroborate these findings.

Influence of polychlorinated biphenyls and organochlorine pesticides on the inflammatory milieu. A systematic review of in vitro, in vivo and epidemiological studies.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are relevant families of persistent organic pollutants, which have been linked to several long-term adverse health effects. The mechanisms of action of these pollutants are still poorly understood. However, there are some evidences suggesting that inflammation might play a key role on their effects. AIM: To systematically synthesize the published in vitro, in vivo and epidemiological data assessing the potential influence of exposure to OCPs and PCBs on the development of an inflammatory milieu. METHODS: A systematic review of peer-reviewed original research papers published until 1st May 2019 was conducted, by using Medline, Web of Science and Scopus databases. A total of 39 articles met the inclusion criteria and were evaluated in this review. RESULTS: The majority of the studies showed significant associations of PCB and OCP exposure with all inflammatory markers measured (n = 30). Some studies showed positive and negative associations (n = 7) and only two studies evidenced negative associations (n = 2). Most of the available evidences came from in vitro and in vivo studies (n = 31), with few epidemiological studies (n = 8). CONCLUSIONS: We found consistent positive associations between exposure to PCBs and OCPs and the development of a pro-inflammatory milieu, with only few discrepancies. However, given the limited epidemiological evidence found, our results warrant further research in order to elucidate the real contribution of these pollutants on the inflammatory processes and subsequent diseases.

Menstrual blood concentrations of parabens and benzophenones and related factors in a sample of Spanish women: An exploratory study.

AIM: To evaluate concentrations of parabens (PBs) and benzophenones (BzPs) in menstrual blood and explore related sociodemographic/lifestyle factors, and to compare between menstrual and peripheral blood concentrations in a subset of samples. MATERIAL AND METHODS: Concentrations of 4 PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP) and butyl-paraben (BuP)] and 6 BzPs [BzP-1, BzP-2, BzP-3, BzP-6, BzP-8 and 4-OH-BzP] were determined in menstrual blood from 57 women and in both menstrual and peripheral blood samples from 12 women, all healthy Spanish women of reproductive age. Socio-demographic characteristics and lifestyle habits [diet and use of cosmetics and personal care products (PCPs)] were gathered using an online questionnaire. Spearman correlation analysis was performed to examine the relationship between menstrual and peripheral blood concentrations, while multivariable linear regression was used to identify potential explanatory variables for menstrual PB and BzP concentrations. RESULTS: Globally, all menstrual blood samples had detectable levels of ≥3 compounds, and 52.6% of the samples contained ≥6 compounds. MeP, PrP, and BzP-3 were the most frequently detected compounds (detection frequencies >90.0%), with median concentrations of 1.41, 0.63, and 1.70 ng/mL of menstrual blood, respectively. Age, the use of PCPs, and consumption of some food items (meat, pasta, cheese, or dairy products) were related to the menstrual blood concentrations of some PBs/BzPs. Serum:menstrual blood ratios of PBs/BzPs ranged from 1.7 to 3.6, with no inter-matrix correlations. CONCLUSIONS: This study reveals, to our knowledge for the first time, the widespread presence of several PBs and BzPs in intimate contact with gynecological tissues, although their concentrations in menstrual blood were not correlated with those in peripheral blood from the same women. These results shed light on the information provided by the menstrual blood as a potential matrix for characterizing exposure to PBs and BzPs, whose consequences for women's reproductive health need to be addressed.

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain.

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n = 144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(ß) = 1.20, p = 0.060] and decreased levels of reduced glutathione (GSH) [exp(ß) = 0.55, p = 0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(ß) = 0.83, exp(ß) = 0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(ß) = 1.73, p-value = 0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(ß) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.

Exploring the radiosensitizing potential of magnetotherapy: a pilot study in breast cancer cells.

Aim: To explore the influence of electromagnetic fields (EMFs) on the cell cycle progression of MDA-MB-231 and MCF-7 breast cancer cell lines and to evaluate the radiosensitizing effect of magnetotherapy during therapeutic co-exposure to EMFs and radiotherapy. Material and methods: Cells were exposed to EMFs (25, 50 and 100 Hz; 8 and 10 mT). In the co-treatment, cells were first exposed to EMFs (50 Hz/10 mT) for 30 min and then to ionizing radiation (IR) (2 Gy) 4 h later. Cell cycle progression and free radical production were evaluated by flow cytometry, while radiosensitivity was explored by colony formation assay. Results: Generalized G1-phase arrest was found in both cell lines several hours after EMF exposure. Interestingly, a marked G1-phase delay was observed at 4 h after exposure to 50 Hz/10 mT EMFs. No cell cycle perturbation was observed after repeated exposure to EMFs. IR-derived ROS production was enhanced in EMF-exposed MCF-7 cells at 24 h post-exposure. EMF-exposed cells were more radiosensitive in comparison to sham-exposed cells. Conclusions: These results highlight the potential benefits of concomitant treatment with magnetotherapy before radiotherapy sessions to enhance the effectiveness of breast cancer therapy. Further studies are warranted to identify the subset(s) of patients who would benefit from this multimodal treatment.

Environmental phenols and parabens in adipose tissue from hospitalized adults in Southern Spain.

Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain). Concentrations of bisphenol-A (BPA), benzophenone-3 (BP-3), triclosan (TCS), three chlorophenols (2,4-DCP, 2,5-DCP and 2,4,5-TCP) and two phenylphenols (2-PP and 4-PP), triclocarban (TCCB) and parabens [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP and i-PrP), butyl- (n-BuP and i-BuP) and benzyl-paraben (BzP)] were analysed in adipose tissue samples from a subcohort of 144 participants. Spearman correlation tests were performed, followed by stepwise multivariable linear regression analyses to assess determinants of the exposure. Detection frequencies and median concentrations were: BPA (86.8%, 0.54 ng/g tissue), BP-3 (79.2%, 0.60 ng/g tissue), TCS (45.8%,

Serum concentrations of organochlorine compounds and predictors of exposure in children living in agricultural communities from South-Eastern Spain.

BACKGROUND: Information on exposure levels to organochlorine compounds (OCs) in child population is limited, despite their greater vulnerability to the adverse health effects of these chemicals. OBJECTIVE: To determine serum concentrations of 10 OCs (including organochlorine pesticides and polychlorinated biphenyls -PCBs-) in children living in agricultural communities from Almería (South-Eastern Spain), and to identify the main predictors of exposure related to socio-economic characteristics, diet and lifestyle. METHODS: A cross-sectional study was conducted on 133 children aged 6-11 years selected from public schools of the study area. OCs compounds were determined in serum samples by GC/ECD. Anthropometric measures were obtained during sample collection. Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and frequency of food consumption, among other relevant factors, was obtained by questionnaires administered to the mothers. RESULTS: Geometric means of serum concentrations (ng/ml) were 0.11 for ß-hexachloro-cyclohexane (ß-HCH), 0.09 for endosulfan, 0.20 for endosulfan-ether, 0.51 for hexachorobenzene (HCB), 0.08 for mirex, 0.06 for oxychlordane, 0.36 for p,p'-DDE, 0.20 for PCB 138, 0.36 for PCB 153, and 0.45 for PCB 180. Percentage of samples above the limit of detection (0.05 ppb) ranged from 32 (ß-HCH) to 100 (HCB). A high variability in OC levels depending on the compound was observed between our results and others found in similar studies carried out in children. Variables related to fish consumption were found to be the major dietary determinant of PCB 138, p,p´-DDE, endosulfan-α, ß-HCH, mirex and oxychlordane levels. CONCLUSIONS: Children participating in this study showed detectable levels of many OC, despite these compounds are no longer used. Their presence in children serum can be explained by their high lipophilicity and environmental persistence, leading to contamination of fatty food. In this line, fish consumption seemed to be the most relevant determinant of OC levels found in our study.

Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals.

Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers.

This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis.

Urinary levels of bisphenol A, benzophenones and parabens in Tunisian women: A pilot study.

Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk.

Serum and adipose tissue as matrices for assessment of exposure to persistent organic pollutants in breast cancer patients.

The aim of this study was to assess differences between two biological matrices (serum and breast adipose tissue) in the evaluation of persistent organic pollutant (POP) exposure in breast cancer patients. The study population consisted of 103 women undergoing surgery for newly diagnosed breast carcinoma in a public hospital in Granada, Southern Spain. Independent variables were gathered from questionnaires and clinical records. POP concentrations were quantified in breast adipose tissue and serum samples. Spearman correlation tests were performed between pairs of POP concentrations and stepwise multivariable linear regression analyses were conducted to assess predictors of concentrations in the two matrices. p,p'- Dichlorodiphenyldichloroethylene (p,p'-DDE) showed the the highest median concentration in both matrices (194.34 and 173.84 ng/g lipid in adipose tissue and serum, respectively). Median wet-basis adipose tissue:serum ratios ranged from 109.34 to 651.62, while lipid-basis ratios ranged from 0.88 to 4.34. In general, we found significant positive correlation coefficients between pairs of POPs in adipose tissue and in serum, which were always higher in adipose tissue. We found positive and statistically significant correlations between serum and adipose tissue concentrations of p,p'-DDE and hexachlorobenzene (HCB) but not of polychlorinated biphenyls (PCBs). Age was positively associated with most POPs in adipose tissue and serum, while the body mass index was positively associated with adipose tissue HCB concentrations and negatively associated with serum PCB-153 and PCB-138 concentrations. Recent weight loss was inversely associated with POP residues in adipose tissue and positively associated with POP residues in serum. Serum HCB and PCB-180 concentrations were lower in patients who had received preoperative chemotherapy. According to our results, serum and adipose tissue POP concentrations in breast cancer patients may be differentially affected by external predictors. Taken together, these findings indicate the need to take account of the individual POP(s) under study and the biological matrix used when relating internal POP exposure to breast cancer disease and to make a careful selection of covariates for adjusting the model.

Levels and predictors of persistent organic pollutants in an adult population from four Spanish regions.

This research aimed to assess serum concentrations of a group of persistent organic pollutants (POPs) in a sample of adults recruited in four different regions from Spain and to assess socio-demographic, dietary, and lifestyle predictors of the exposure. The study population comprised 312 healthy adults selected from among controls recruited in the MCC-Spain multicase-control study. Study variables were collected using standardized questionnaires, and pollutants were analyzed by means of gas chromatography with electron capture detection. Multivariable analyses were performed to identify predictors of log-transformed pollutant concentrations, using combined backward and forward stepwise multiple linear regression models. Detection rates ranged from 89.1% (hexachlorobenzene, HCB) to 93.6% (Polychlorinated biphenyl-153 [PCB-153]); p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) showed the highest median concentrations (1.04ng/ml), while HCB showed the lowest (0.24ng/ml). In the multivariable models, age was positively associated with HCB, p,p'-DDE, and PCB-180. BMI was associated positively with p,p'-DDE but negatively with PCB-138. Total accumulated time residing in an urban area was positively associated with PCB-153 concentrations. The women showed higher HCB and lower p,p'-DDE concentrations versus the men. Notably, POP exposure in our study population was inversely associated with the breastfeeding received by participants and with the number of pregnancies of their mothers but was not related to the participants' history of breastfeeding their children or parity. Smoking was negatively associated with HCB and PCB-153 concentrations. Consumption of fatty foods, including blue fish, was in general positively associated with POP levels. Although POP environmental levels are declining worldwide, there is a need for the continuous monitoring of human exposure in the general population. The results of the present study confirm previous findings and point to novel predictors of long-term exposure to persistent organic pollutants.

Serum levels of persistent organic pollutants and predictors of exposure in Tunisian women.

INTRODUCTION: In spite of the international consensus on the human health risks associated with exposure to persistent organic pollutants (POPs), the Tunisian population is suspected to have been inadvertently exposed to POPs over the last decades. OBJECTIVES: The aim of this study was to evaluate POP concentrations in the serum of a subset of 54 Tunisian women and to identify some socio-demographic and dietary predictors of exposure to POPs. RESULTS: Of the ten POPs analyzed, three polychlorinated biphenyl (PCB) congeners (-138, -153 and -180), and two organochlorine pesticides (OCPs), HCB and p,p'-DDE, showed frequencies ranging from 98 to 100%. Serum median concentrations of PCB congeners (-138, -153 PCB-180) were 26.08, 119.1 and 29.84 ng/g lipid, respectively, and median concentrations of HCB and p,p'-DDE were 19.98 and 127.59 ng/g lipid, respectively. Age was positively correlated with serum levels of selected POPs. Women living in northern Tunisia showed higher serum levels of all PCBs. Working outside home and cereal consumption were positively associated to serum levels of p,p'-DDE. The duration of the lactation was also related to lower serum levels of p,p'-DDE and HCB. CONCLUSION: The levels of exposure to POPs found warrant a biomonitoring program in order to identify routes of exposure and population groups at higher risk. This program will help to establish prevention policies and to determine the association between exposure to POPs and chronic diseases.

Matrix metalloproteinases: potential therapy to prevent the development of second malignancies after breast radiotherapy.

Radiotherapy is widely used in the treatment of patients with breast cancer, but ionizing radiation-induced carcinogenesis has been described in several studies. Matrix metalloproteinases (MMPs) are a wide family of proteases secreted by tumour and microenvironmental cells that are directly linked with invasion and metastasis through complete extracellular matrix (ECM) breakage. In the past decade, MMPs have been associated with other carcinogenesis steps, including tumour growth and angiogenesis promotion. Moreover, in vitro studies have demonstrated an enhanced migration, invasiveness, and angiogenic ability of cancer cells after radiation exposure through an increase in MMP activity. These findings are consistent with clinical observations of breast cancer metastases raised in bone, lung and brain tissues after radiotherapy. The aim of this review was to analyse the current state of research on MMPs and report new insights into the potential of MMP-targeted therapy in combination with radiotherapy to decrease the risk of radiation-induced second malignancies and to improve the overall survival of breast cancer patients.