Health & Environmental Research Online (HERO)


Benzo(a)pyrene (BaP)


1,930 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Identification and Functional Studies of a New Nrf2 Partner IQGAP1: A Critical Role in the Stability and Transactivation of Nrf2

Authors: Kim, JH; Xu, EY; Sacks, DB; Lee, J; Shu, L; Xia, B; Kong, AN (In Press) HERO ID: 1578643

[Less] Abstract Aims: Nuclear factor-erythroid-related factor 2 (Nrf2) is a critical transcriptional factor . . . [More] Abstract Aims: Nuclear factor-erythroid-related factor 2 (Nrf2) is a critical transcriptional factor that is used in regulating cellular defense against oxidative stress. This study is aimed at investigating new interacting protein partners of Nrf2 using One-strep tag pull-down coupled with LTQ Orbitrap LC/MS/MS, and at examining the impact on Nr2 signaling by the newly identified IQ motif containing GTPase activating protein 1 (IQGAP1). Results: Using the One-strep tag pull-down and LTQ Orbitrap LC/MS/MS, we identified IQGAP1 as a new Nrf2 interacting partner. Direct interactions between IQGAP1 and Nrf2 proteins were verified using in vitro glutathione S-transferase (GST) pull-down, transcription/translation assays, and in vivo utilizing Nrf2 overexpressing cells. Coexpression of Dsredmono-IQGAP1 and eGFP-Nrf2 increased the stability of eGFP-Nrf2 and enhanced the expression of Nrf2-target gene heme oxygenase-1 (HO-1). To confirm the functional role of IQGAP1 on Nrf2, knock-downed IQGAP1 using siIQGAP1 attenuated the expression of endogenous Nrf2, HO-1 proteins, and Nrf2-target genes GSTpi, GCLC, and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Furthermore, the stability of Nrf2 was dramatically decreased in IQGAP1-deficient mouse embryonic fibroblast (MEF) cells. Since IQGAP1 signaling could be mediated by calcium, treating the cells with calcium showed the translocation of IQGAP1/Nrf2 complex into the nucleus, suggesting that IQGAP1 may play a critical role in Nrf2 stability. Interestingly, consistent with calcium signaling for IQGAP1, treating the cells with calcium functionally enhanced Nrf2-mediated antioxidant responsive element-transcription activity and enhanced the expression of the endogenous Nrf2-target gene HO-1. Innovation: In the aggregate, our current study identifies and functionally characterizes a new Nrf2 partner protein IQGAP1, which may contribute to Nrf2's regulation of antioxidant enzymes such as HO-1. Conclusion: IQGAP1 may play a critical role in the stability and transactivation of Nrf2. Antioxid. Redox Signal. 00, 000-000.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Aryl Hydrocarbon Receptor-Mediated impairment of chondrogenesis and fracture healing by cigarette smoke and benzo(a)pyrene

Authors: Kung, MH; Yukata, K; O'Keefe, RJ; Zuscik, MJ (In Press) Journal of Cellular Physiology. HERO ID: 1010816

[Less] The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since . . . [More] The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since cigarette smoke (CS) contains numerous polycyclic aromatic hydrocarbons (PAHs), and since dioxins impair bone formation in vivo via the Aryl Hydrocarbon Receptor (AHR), we investigated the impact of PAH/AHR signaling on chondrogenesis and on healing in a mouse tibial fracture model. We established that CS activates AHR signaling in fractures by up-regulating the AHR target gene cytochrome p4501A1 (Cyp1A1). For in vitro studies, we employed the mouse limb bud micromass chondrogenesis model. After confirming that chondrocytes express AHR during differentiation, we treated cells with a prototypical PAH found in CS, benzo(α)pyrene (BaP), or cigarette smoke extract (CSE). Both BaP and CSE both strongly inhibited chondrogenesis in mesenchymal cells generated from E11 limb buds, with BaP also accelerating chondrocyte hypertrophy in cultures generated from E12 limb buds. Detection of DNA adducts in the BaP-treated cultures suggests that the distinct phenotypic effects of BaP may be due to the formation of reactive metabolites. Blockade of AHR signaling with the AHR antagonist MNF reverses the effects of BaP, but not CSE, suggesting that CSE inhibition of chondrogenesis is AHR-independent. Correlating with these results, tibial fracture calluses from BaP-treated mice were smaller and contained less mineralized tissue than vehicle controls. Overall, BaP is identified as a potent inhibitor of chondrogenesis in vitro with correlated effects on fracture healing similar to those of CS itself, suggesting a basis for PAHs as key compounds in the influence of CS on fracture repair. J. Cell. Physiol. © 2011 Wiley-Liss, Inc.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Green tea extract markedly lowers the lymphatic absorption and increases the biliary secretion of (14)C-benzo[a]pyrene in rats

Authors: Kim, J; Koo, SI; Noh, SK (In Press) Journal of Nutritional Biochemistry. HERO ID: 1011018

[Less] Previously, we have shown that green tea extract (GTE) lowers the intestinal absorption of lipids and . . . [More] Previously, we have shown that green tea extract (GTE) lowers the intestinal absorption of lipids and lipophilic compounds in rats. This study was conducted to investigate whether GTE inhibits the intestinal absorption and biliary secretion of benzo[a]pyrene (BaP), an extremely lipophilic potent carcinogen, present in foods as a contaminant. Male rats with lymph or bile duct cannula were infused at 3.0 ml/h for 8 h via a duodenal catheter with lipid emulsion containing (14)C-BaP with or without GTE in PBS buffer. Lymph and bile were collected hourly for 8 h. The (14)C-radioactivities in lymph, bile and intestine were determined and expressed as % dose infused. Results showed that GTE drastically lowered the lymphatic absorption of (14)C-BaP (7.6±3.2% in GTE-infused vs. 14.4±2.7% dose/8 h in control rats), with a significantly higher amount of (14)C-radioactivity present in the small intestinal lumen and cecum in rats infused with GTE. GTE also markedly increased the hourly rate (3.9±0.1% dose/h in GTE-infused vs. 3.0±0.1% dose/h in control rats) and the total biliary secretion of (14)C-BaP (31.5±0.8% dose/8 h in GTE-infused vs. 24.3±0.4% dose/8 h in control rats). The findings provide first direct evidence that GTE has a profound inhibitory effect on the intestinal absorption of BaP and promotes the excretion of absorbed BaP via the biliary route. Further studies are warranted to investigate whether green tea could be recommended as a dietary means of ameliorating the toxicity and carcinogenic effect of BaP.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Dose-response modeling with summary data from developmental toxicity studies

Authors: Fox, JR; Hogan, KA; Davis, A (2016) Risk Analysis. HERO ID: 3392311

[Less] Dose-response analysis of binary developmental data (e.g., implant loss, fetal abnormalities) is best . . . [More] Dose-response analysis of binary developmental data (e.g., implant loss, fetal abnormalities) is best done using individual fetus data (identified to litter) or litter-specific statistics such as number of offspring per litter and proportion abnormal. However, such data are not often available to risk assessors. Scientific articles usually present only dose-group summaries for the number or average proportion abnormal and the total number of fetuses. Without litter-specific data, it is not possible to estimate variances correctly (often characterized as a problem of overdispersion, intralitter correlation, or “litter effect”). However, it is possible to use group summary data when the design effect has been estimated for each dose group. Previous studies have demonstrated useful dose-response and trend test analyses based on design effect estimates using litter-specific data from the same study. This simplifies the analysis but does not help when litter-specific data are unavailable. In the present study, we show that summary data on fetal malformations can be adjusted satisfactorily using estimates of the design effect based on historical data. When adjusted data are then analyzed with models designed for binomial responses, the resulting benchmark doses are similar to those obtained from analyzing litter-level data with nested dichotomous models.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki-67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus

Authors: He, J; Ji, X; Li, Y; Xue, X; Feng, G; Zhang, H; Wang, H; Gao, M (2016) Experimental and Toxicologic Pathology 68:149-156. HERO ID: 3160685

[Less] Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous . . . [More] Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki-67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region-difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki-67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Testicular and epididymal toxicity induced by benzo(a) pyrene, alcohol, and their combination in Wistar rats

Authors: Reddy, KP; Reddy, PS (2016) Toxicology Research 5:420-433. HERO ID: 3123583

[Less] Alcoholism and cigarette smoking are pervasive problems that have been implicated in human health. In . . . [More] Alcoholism and cigarette smoking are pervasive problems that have been implicated in human health. In this study, independent and combinative toxicities of alcohol and benzo(a) pyrene (BaP) were tested for reproductive toxicity in rats. Male Wistar rats were exposed to BaP (100 mu g per kg body weight) on alternative days and alcohol (2 g per kg body weight per day) daily, either individually or in combination for 60 days. Exposure to BaP or alcohol significantly decreased the fertility index and reduced the number of implantations associated with elevated pre- and post-implantation losses. The relative weights of testes, epididymis, seminal vesicles, and prostate gland were significantly decreased in BaP or alcohol administered rats. Exposure to BaP or alcohol significantly decreased daily sperm production, sperm density, percentages of motile, viable, HOS-tail swelled sperm, testicular 3 beta- and 17 beta-hydroxysteroid dehydrogenase activity levels, mRNA levels of steroidogenic acute regulatory protein, and serum testosterone levels. Further, in silico studies revealed the binding of BaP at the hydrophobic tunnel of StAR protein. Additional studies disclosed stable interactions of BaP with the amide group of ASN150 and the hydroxyl group of THR263 by forming three hydrogen bonds. Our results also showed that treatment of rats with BaP or alcohol caused a marked increase in levels of superoxide anions, hydrogen peroxide, and lipid peroxidation in testis and epididymis. Conversely, glutathione levels and activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in testis as well as epididymis decreased significantly in the experimental rats. Under the same conditions, increased fragmented DNA levels were observed in sperm. The results of the present study indicate that exposure to BaP or alcohol adversely affected the male reproductive functions, which may be, at least in part, due to androgen deficiency and/or oxidative stress-related mechanisms. Consistently, the present results also showed higher reproductive toxicity upon exposure to combinations of BaP and alcohol than upon their individual treatments. Therefore, this combination was classified as additive and synergistic responses of BaP and alcohol.

Journal Article
Journal Article

Postmenopausal Breast Cancer Risk in Relation to Antibodies Specific to Benzo[a]Pyrene, Estradiol and Progesterone

Authors: Glushkov, A; Polenok, E; Kostyanko, M; Antonov, A; Verzhbitskaya, N; Vafin, I; Ragozhina, S (2016) 9:e4212. HERO ID: 3378315

[Less] BACKGROUND: Antibodies might protect against low doses of environmental carcinogens . . . [More] BACKGROUND: Antibodies might protect against low doses of environmental carcinogens by decreasing systemic uptake, activation of metabolic pathways, and redistribution of carcinogens within the organism. The features of antibody formation in relation to environmental carcinogens and sex steroids under natural conditions should be determined to identify breast cancer risk, then to develop cancer immune prevention strategies.

OBJECTIVES: The purpose of this study was to investigate antibodies specifications to benzo(a)pyrene, estradiol and progesterone in postmenopausal women with invasive breast cancer.

PATIENTS AND METHODS: A semi-quantitative non-competitive immunoassay of IgG antibodies to benzo(a)pyrene (IgG-Bp), estradiol (IgG-Es), and progesterone (IgG-Pg) has conducted. The assay has performed on 322 serum samples from patients with breast cancer and 179 serum samples from healthy postmenopausal women by using low-molecular-weight Bp, Es, and Pg conjugated with bovine serum albumin. ROC analysis has also conducted to determine the odds ratio (OR).

RESULTS: Combination of the high levels of IgG-Bp and IgG-Es without IpG-Pg was more frequent in breast cancer patients than that in healthy women, and the OR has increased to 3.8. Combination of the high levels of IgG-Pg with high levels of both IgG-Bp and IgG-Es were significantly more frequent in breast cancer patients (36.9%) than that in healthy women (5.6%), and the OR increased to 11.7. These differences have peculiarly expressed in breast cancer patients with hormone status ER+/PR- (OR = 26.7). The minimum OR (0.4) has obtained at low levels of the three antibodies.

CONCLUSIONS: Immunoassay of antibodies against environmental carcinogens and sex steroid hormones could use to detect breast cancer risk. Induction of antibodies against Bp for cancer immunoprevention could lead to antibody formation against steroid hormones, thereby increasing breast cancer risk.

Technical Report
Technical Report

The priority list of hazardous substances that will be the subject of toxicological profiles

Author: ATSDR (2016) Atlanta, GA: CDC Agency for Toxic Substances and Disease Registry. [ATSDR Tox Profile] HERO ID: 3378161

[Less] The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) section 104 (i), . . . [More] The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) section 104 (i), as amended by the Superfund Amendments and Reauthorization Act (SARA), requires ATSDR and the EPA to prepare a list, in order of priority, of substances that are most commonly found at facilities on the National Priorities List (NPL) and which are determined to pose the most significant potential threat to human health due to their known or suspected toxicity and potential for human exposure at these NPL sites. CERCLA also requires this list to be revised periodically to reflect additional information on hazardous substances.

This substance priority list is revised and published on a 2-year basis, with a yearly informal review and revision. (No list was published in 2009 while ATSDR transitioned to a new agency science database.) Each substance on the list is a candidate to become the subject of a toxicological profile prepared by ATSDR. The listing algorithm prioritizes substances based on frequency of occurrence at NPL sites, toxicity, and potential for human exposure to the substances found at NPL sites.

It should be noted that this priority list is not a list of "most toxic" substances, but rather a prioritization of substances based on a combination of their frequency, toxicity, and potential for human exposure at NPL sites.

Thus, it is possible for substances with low toxicity but high NPL frequency of occurrence and exposure to be on this priority list. The objective of this priority list is to rank substances across all NPL hazardous waste sites to provide guidance in selecting which substances will be the subject of toxicological profiles prepared by ATSDR.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Exposures to road traffic, noise, and air pollution as risk factors for type 2 diabetes: A feasibility study in Bulgaria

Authors: Dzhambov, AM; Dimitrova, DD (2016) Noise and Health 18:133-142. HERO ID: 3359237

[Less] Type 2 diabetes mellitus (T2DM) is a growing public health problem in Bulgaria. While individual and . . . [More] Type 2 diabetes mellitus (T2DM) is a growing public health problem in Bulgaria. While individual and lifestyle determinants have been researched; till date there has been no study on environmental risks such as road traffic, noise, and air pollution. As a first step toward designing a large-scale population-based survey, we aimed at exploring the overall associations of prevalent T2DM with exposures to road traffic, noise, and air pollution. A total of 513 residents of Plovdiv city, Bulgaria were recruited. Individual data on self-reported doctor-diagnosed T2DM and confounding factors were linked to objective and self-rated exposure indicators. Logistic and log-link Poisson regressions were conducted. In the fully adjusted logistic models, T2DM was positively associated with exposures to L(den) 71-80 dB (odds ratio (OR) = 4.49, 95% confidence interval (CI): 1.38, 14.68), fine particulate matter (PM) 2.5 25.0-66.8 μg/m 3 (OR = 1.32, 95% CI: 0.28, 6.24), benzo alpha pyrene 6.0-14.02 ng/m 3 (OR = 1.76, 95% CI: 0.52, 5.98) and high road traffic (OR = 1.40, 95% CI: 0.48, 4.07). L(den) remained a significant risk factor in the: Poisson regression model. Other covariates with consistently high multivariate effects were age, gender, body mass index, family history of T2DM, subjective sleep disturbance, and especially bedroom location. We concluded that residential noise exposure might be associated with elevated risk of prevalent T2DM. The inferences made by this research and the lessons learned from its limitations could guide the designing of a longitudinal epidemiological survey in Bulgaria.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Association of environmental benzo[a]pyrene exposure and DNA methylation alterations in hepatocellular carcinoma: A Chinese case-control study

Authors: Tian, M; Zhao, B; Zhang, Jie; Martin, FL; Huang, Q; Liu, L; Shen, H (2016) Science of the Total Environment 541:1243-1252. HERO ID: 3124556

[Less] Epidemiological studies implicate environmental risk factors and epigenetic alterations in the multistage . . . [More] Epidemiological studies implicate environmental risk factors and epigenetic alterations in the multistage process of hepatocellular carcinoma (HCC) development. However, associations between environmental factors and DNA methylation of tumour suppressor genes (TSGs) in HCC development remain ambiguous. Understanding how possible interactions influence risk may provide insights into the complexity of hepato-carcinogenesis. For this study, blood samples were collected from HCC patients (n=90) and healthy volunteers (n=99) from Xiamen (China) and data for selected environmental risk factors [e.g., benzo[a]pyrene (B[a]P), hepatitis B or C virus (HBV or HCV) infection, smoking and alcohol consumption] were recorded; factors identified as significantly higher (P<0.05) amongst case subjects compared to controls were identified. In order to assess associations for epigenetic alterations and HCC risk factors, serum DNA methylation of TSGs was quantified using high-resolution melting (HRM) analysis. Our results clearly indicate elevated methylation patterns for detoxification gene [glutathione-S-transferase Pi (GSTP)] promoter regions in cases compared to control subjects. Additionally, GSTP promoter hypermethylation and B[a]P diol epoxide-albumin (BPDE-Alb) were positively correlated with HCC incidence. Our epidemiological and in vitro cell model studies indicated that GSTP promoter DNA methylation regulates this gene's expression. Moreover, GSTP also plays an important role in B[a]P detoxification and potential protective role against B[a]P-induced liver cell toxicity and hepato-carcinogenesis.