Health & Environmental Research Online (HERO)


Benzo(a)pyrene (BaP)


1,857 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

Polycyclic aromatic hydrocarbons: from metabolism to lung cancer

Authors: Moorthy, B; Chu, C; Carlin, DJ (2015) Toxicological Sciences 145:5-15. HERO ID: 2947777

[Less] Excessive exposure to polycyclic aromatic hydrocarbons (PAHs) often results in lung cancer, a disease . . . [More] Excessive exposure to polycyclic aromatic hydrocarbons (PAHs) often results in lung cancer, a disease with the highest cancer mortality in the United States. After entry into the lung, PAHs induce phase I metabolic enzymes such as cytochrome P450 (CYP) monooxygenases, i.e. CYP1A1/2 and 1B1, and phase II enzymes such as glutathione S-transferases, UDP glucuronyl transferases, NADPH quinone oxidoreductases (NQOs), aldo-keto reductases (AKRs), and epoxide hydrolases (EHs), via the aryl hydrocarbon receptor (AhR)-dependent and independent pathways. Humans can also be exposed to PAHs through diet, via consumption of charcoal broiled foods. Metabolism of PAHs through the CYP1A1/1B1/EH pathway, CYP peroxidase pathway, and AKR pathway leads to the formation of the active carcinogens diol-epoxides, radical cations, and o-quinones. These reactive metabolites produce DNA adducts, resulting in DNA mutations, alteration of gene expression profiles, and tumorigenesis. Mutations in xenobiotic metabolic enzymes, as well as polymorphisms of tumor suppressor genes (e.g. p53) and/or genes involved in gene expression (e.g. X-ray repair cross-complementing proteins), are associated with lung cancer susceptibility in human populations from different ethnicities, gender, and age groups. Although various metabolic activation/inactivation pathways, AhR signaling, and genetic susceptibilities contribute to lung cancer, the precise points at which PAHs induce tumor initiation remain unknown. The goal of this review is to provide a current state-of-the-science of the mechanisms of human lung carcinogenesis mediated by PAHs, the experimental approaches used to study this complex class of compounds, and future directions for research of these compounds.

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

Dermatological exposure to coal tar and bladder cancer risk: a case-control study

Authors: Roelofzen, JH; Aben, KK; Van de Kerkhof, PC; Van der Valk, PG; Kiemeney, LA (2015) Urologic Oncology 33:20.e19-20.e22. HERO ID: 2947820

[Less] OBJECTIVE: Coal tar ointments are used as treatment of various skin diseases, especially . . . [More] OBJECTIVE: Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer.

MATERIAL AND METHODS: A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking.

RESULTS: The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93-2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61-0.90).

CONCLUSION: This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice.

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

Levels of polycyclic aromatic hydrocarbons in maternal serum and risk of neural tube defects in offspring

Authors: Wang, B; Jin, L; Ren, A; Yuan, Y; Liu, J; Li, Z; Zhang, L; Yi, D; Wang, LL; Zhang, Y; Wang, X; Tao, S; Finnell, RH (2015) Environmental Science and Technology 49:588-596. HERO ID: 3378313

[Less] Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, and have been reported . . . [More] Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, and have been reported to be a risk factor for human neural tube defects (NTDs). We investigated the relationship between PAH concentrations in maternal serum and NTD risk in offspring using a case-control study design, and explored the link between PAH concentrations to household energy usage characteristics and life styles. One hundred and seventeen women who had NTD-affected pregnancies (cases) and 121 women who delivered healthy infants (controls) were recruited in Northern China. Maternal blood samples were collected at pregnancy termination or at delivery. Twenty-seven PAHs were measured by gas chromatography-mass spectrometry. The concentrations of 13 individual PAHs detected were significantly higher in the cases than in the controls. Clear dose-response relationships between concentrations of most individual PAHs and the risk of total NTDs or subtypes were observed, even when potential covariates were adjusted for. High-molecular-weight PAHs (H-PAHs) showed higher risk than low-molecular-weight PAHs (L-PAHs). No associations between PAH concentrations and indoor life styles and energy usage characteristics were observed. It was concluded that maternal exposure to PAHs was associated with an increased risk of NTDs, and H-PAHs overall posed a higher risk for NTDs than L-PAHs.

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

Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer

Authors: Geetha, T; Kapila, M; Prakash, O; Deol, PK; Kakkar, V; Kaur, IP (2015) Journal of Drug Targeting 23:159-169. HERO ID: 3121800

[Less] Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, . . . [More] Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

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

Comparison of the acute effects of benzo-a-pyrene on adult zebrafish (Danio rerio) cardiorespiratory function following intraperitoneal injection versus aqueous exposure

Authors: Gerger, CJ; Weber, LP (2015) Aquatic Toxicology 165:19-30. HERO ID: 3121801

[Less] Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. PAH exposure causes . . . [More] Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. PAH exposure causes developmental toxicity in multiple fish species, while acute adult fish toxicity is thought to be minimal. The literature increasingly suggests sublethal PAH effects may occur, but differences in exposure route may confound conclusions. We hypothesized that acute PAH exposure in adult fish will cause cardiorespiratory impairment that will not differ with exposure route. In order to investigate this hypothesis, adult zebrafish (Danio rerio) were injected intraperitoneal (i.p.) twice with increasing concentrations of the prototypical PAH, benzo-a-pyrene (BaP; 0.1, 10, and 1000μg/kg) or exposed aqueously (static, renewal at 24h; 16.2 and 162μg/L) for 48h and compared to corresponding dimethylsulfoxide controls. No mortalities or significant effects on weight of the fish were noted at any exposure concentration or route. At 48h, fish were subjected to swimming tests with concurrent oxygen consumption measurement (n=10 fish/treatment) or echocardiography (n=12 fish/treatment). Oxygen consumption (MO2) was increased at three swimming speeds in BaP-injected groups compared to control (p<0.01 in Fisher's LSD tests after two-way ANOVA). In contrast, aqueously BaP-exposed fish showed increased MO2 under only basal conditions. Despite increased oxygen demand, ventricular heart rate was significantly decreased in BaP-exposed fish, both injected and aqueously-exposed. Analysis of BaP body burdens in fish tissue allowed for identification of an overlapping dose group between exposure routes, through which comparisons of cardiorespiratory toxicity were then made. This comparison revealed most effects were similar between the two exposures routes, although minor differences were noted. At similar BaP body burdens, injected fish suffered from more severe bradycardia than aqueously exposed fish and had greater levels of increases in cytochrome P4501A (CYP1A) mRNA levels in liver and heart tissue compared to aqueous exposed fish. In conclusion, acute BaP exposure in adult zebrafish had negative effects on cardiorespiratory function. Differences in effect between exposure routes were attributed primarily to differences in bioavailability, since overall, similar effects were noted between the two exposure routes when similar BaP body burdens were achieved.

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

Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study

Authors: Chepelev, NL; Moffat, ID; Labib, S; Bourdon-Lacombe, J; Kuo, B; Buick, JK; Lemieux, F; Malik, AI; Halappanavar, S; Williams, A; Yauk, CL (2015) Critical Reviews in Toxicology 45:44-52. [Review] HERO ID: 2944147

[Less] The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable . . . [More] The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable advantages relative to traditional toxicity testing methods. The advantages include increased throughput, increased mechanistic data, and significantly reduced costs. However, precisely how toxicogenomics data can be used to support human health risk assessment (RA) is unclear. In a companion paper ( Moffat et al. 2014 ), we present a case study evaluating the utility of toxicogenomics in the RA of benzo[a]pyrene (BaP), a known human carcinogen. The case study is meant as a proof-of-principle exercise using a well-established mode of action (MOA) that impacts multiple tissues, which should provide a best case example. We found that toxicogenomics provided rich mechanistic data applicable to hazard identification, dose-response analysis, and quantitative RA of BaP. Based on this work, here we share some useful lessons for both research and RA, and outline our perspective on how toxicogenomics can benefit RA in the short- and long-term. Specifically, we focus on (1) obtaining biologically relevant data that are readily suitable for establishing an MOA for toxicants, (2) examining the human relevance of an MOA from animal testing, and (3) proposing appropriate quantitative values for RA. We describe our envisioned strategy on how toxicogenomics can become a tool in RA, especially when anchored to other short-term toxicity tests (apical endpoints) to increase confidence in the proposed MOA, and emphasize the need for additional studies on other MOAs to define the best practices in the application of toxicogenomics in RA.

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

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Authors: Moffat, I; Chepelev, NL; Labib, S; Bourdon-Lacombe, J; Kuo, B; Buick, JK; Lemieux, F; Williams, A; Halappanavar, S; Malik, AI; Luijten, M; Aubrecht, J; Hyduke, DR; Fornace, AJ; Swartz, CD; Recio, L; Yauk, CL (2015) Critical Reviews in Toxicology 45:1-43. [Review] HERO ID: 2947764

[Less] Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic . . . [More] Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.

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

Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models

Authors: Li, E; Xu, Z; Zhao, H; Sun, Z; Wang, L; Guo, Z; Zhao, Y; Gao, Z; Wang, Q (2015) Oncotarget 6:8900-8913. HERO ID: 3121819

[Less] We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation . . . [More] We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

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

Vehicular traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: The Long Island Breast Cancer Study Project (LIBCSP)

Authors: Mordukhovich, I; Beyea, J; Herring, AH; Hatch, M; Stellman, SD; Teitelbaum, SL; Richardson, DB; Millikan, RC; Engel, LS; Shantakumar, S; Steck, SE; Neugut, AI; Rossner, P; Santella, RM; Gammon, MD (2015) Environmental Health Perspectives 124:30-38. HERO ID: 3021352

[Less] BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, . . . [More] BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure.

OBJECTIVES: Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence.

METHODS: Residential histories of 1,508 breast cancer cases and 1,556 controls were assessed in a population-based investigation conducted in 1996-1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960-1995 were reconstructed using a model previously shown to generate estimates that are consistent with measured soil PAHs, PAH-DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression.

RESULTS: The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960-1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake (1.46 (0.89, 2.40), but not among those with high intake (0.92 (0.53, 1.60)). Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic-breast cancer association was higher for those with estrogen/progesterone-negative tumors (1.67 (0.91, 3.05) relative to controls), but lower among all other tumor subtypes (0.80 (0.50, 1.27) compared with controls).

CONCLUSIONS: In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise.

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

Changes in Peripheral Blood Monocytes and Liver Macrophages in Male Rats after Benzo(a)pyrene Injection

Authors: Kolesnikov, SI; Michurina, SV; Arkhipov, SA (2015) Bulletin of Experimental Biology and Medicine 158:735-738. HERO ID: 3121816

[Less] Intraperitoneal injections of benzo(a)pyrene to male rats in a total dose of 60 mg/kg modified the production . . . [More] Intraperitoneal injections of benzo(a)pyrene to male rats in a total dose of 60 mg/kg modified the production of ROS and the phagocytic potential of blood monocytes by modulating their potential bactericidal activity. The lysosomal system (particularly the secondary lysosomes) of liver macrophages was activated, which promoted fusion of the hydrolytic potentials of macrophages and monocytes. These results indicated that the toxin modulated the cellular immune homeostasis and the level of general nonspecific resistance.