Synergistic enhancement of H2O2 production in human epidermoid carcinoma cells by Benzo[a]pyrene and ultraviolet A radiation☆☆This research was supported by a Grant from the National Institute of Environmental Health Sciences (ES09843) and by a Dermatology Foundation Grant awarded to Huachen Wei.

Shyong, Eileen Q.; Lu, Yuhun; Goldstein, Amy E.; Lebwohl, Mark; Wei, Huachen

doi:10.1016/s0041-008x(03)00018-8

Cited by 33 publications

(7 citation statements)

References 18 publications

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“…At low concentrations, pyrene caused stimulation of HaCaT proliferation while 1-HP and 1-AP inhibit cell proliferation; and at 10μg/mL, pyrene, 1-AP and 1-HP significantly inhibit HaCaT proliferation (Figures 2–4). It is an established fact that substituted PAH derivatives are more soluble than their parent compounds, and are therefore more accessible and toxic to the cells [10]. This could explain why, at low concentrations, the substituted PAHs were more toxic to the HaCaT cells than the parent compound pyrene.…”

Section: Resultsmentioning

confidence: 99%

“…Once more, the end point is cell death, either by necrosis or apoptosis. It has been found that UV-A irradiated benzo[a]pyrene causes cellular reactions to occur that heighten DNA damage [10]. Such exposure to human epidermoid carcinoma cells and human keratinocytes results in a 5-fold increase in the production of H 2 O 2 , which is known to cause significant DNA damage [12–13].…”

Section: Discussionmentioning

confidence: 99%

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Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

Ekunwe

Hunter

Hwang

2005

IJERPH

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Over the past several years, a great deal of interest has been focused on the harmful effects of ultraviolet (UV) radiation to human skin. UV light has been implicated in aging, sunburn and skin cancer. Few studies, however, have been done to determine the effects that UV light, in conjunction with other environmental contaminants, may have on human skin. Polycyclic Aromatic Hydrocarbons (PAHs) are a class of compounds that have been reported to be toxic, mutagenic and carcinogenic to many eukaryotic organisms. UV light is also known to increase the toxicity of PAHs through photo-activation and photo-modification. The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr), 1-aminopyrene (1-AP) and 1-hydroxypyrene (1-HP) on human keratinocytes, the skin primary site of UV irradiated PAH exposure. Our findings indicate that simultaneous treatment of human keratinocyte cell line, HaCaT, with 1.0μg/ml pyrene, 1-AP or 1-HP and 3.9 J/cm2/min UV-A light resulted in significant inhibition of cell proliferation. Approximately 100% of the cells died in the case of UV-A irradiated 1-AP and 1-HP. In the case of UV-A irradiated pyrene, more than 70% of the cells died, indicating that UV-A is able to transform these PAHs into more harmful intermediates.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

Ekunwe

Hunter

Hwang

2005

IJERPH

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“…Interestingly, TCDD is known to induce IL-1β expression in human keratinocytes [80] and several environmental AHR agonists, such as TCDD and PAHs, may induce ROS formation by stimulating CYP1, aldo-keto reductase, or NADPH oxidase activities [81,82,83,84]. In addition, in co-exposure scenarios, PAHs and FICZ may serve as a photosensitizer for UVA radiation, resulting in a profound generation of ROS and associated oxidative damage and signaling responses [85,86,87]. In FICZ-treated fibroblasts, the usage of pharmacological inhibitors confirmed that the AHR-dependent upregulation of MMP-1 and MMP-3 is mediated through MEK-ERK signaling [75], pointing to an involvement of AP-1.…”

Section: Ahr and Extrinsic Skin Agingmentioning

confidence: 99%

“…Apart from UVA-related phototoxicity of PAHs [86,87], the AHR-dependent upregulation of CYP1 isoforms in UVB radiation-exposed skin may sensitize cells to PAH-mediated DNA adduct formation, thereby enhancing the risk of respectively exposed people, e.g., roofers and roadmen, to develop SCCs. In fact, a study assessing the influence of UVB irradiation and crude coal tar treatment on cutaneous CYP1 enzyme activity and BaP metabolism revealed that crude coal tar, as well as UVB exposure alone, induced CYP1 activity and BaP oxidation.…”

Section: Ahr and Skin Cancermentioning

confidence: 99%

Role of the Aryl Hydrocarbon Receptor in Environmentally Induced Skin Aging and Skin Carcinogenesis

Vogeley

Esser

Tüting

et al. 2019

IJMS

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The skin is constantly exposed to a variety of environmental threats, including solar electromagnetic radiation, microbes, airborne particulate matter, and chemicals. Acute exposure to these environmental factors results in the activation of different signaling pathways that orchestrate adaptive stress responses to maintain cell and tissue homeostasis. Chronic exposure of skin to these factors, however, may lead to the accumulation of damaged macromolecules and loss of cell and tissue integrity, which, over time, may facilitate aging processes and the development of aging-related malignancies. One transcription factor that is expressed in all cutaneous cells and activated by various environmental stressors, including dioxins, polycyclic aromatic hydrocarbons, and ultraviolet radiation, is the aryl hydrocarbon receptor (AHR). By regulating keratinocyte proliferation and differentiation, epidermal barrier function, melanogenesis, and immunity, a certain degree of AHR activity is critical to maintain skin integrity and to adapt to acute stress situations. In contrast, a chronic activation of cutaneous AHR signaling critically contributes to premature aging and the development of neoplasms by affecting metabolism, extracellular matrix remodeling, inflammation, pigmentation, DNA repair, and apoptosis. This article provides an overview of the detrimental effects associated with sustained AHR activity in chronically stressed skin and pinpoints AHR as a promising target for chemoprevention.

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“…However, in a more recent study, this effect was partly attributed to activation of the arylhydrocarbon receptor (AhR), which was induced in parallel by both BPQ metabolites [ 101 ]. There is further evidence that BP enhances H 2 O 2 formation synergistically with UVA-radiation and promotes formation of 8-OHdG lesions in DNA of epidermal cells [ 102 ]. In HepG2 cells, BP triggered an antioxidant response, including elevated levels of GSH [ 103 ].…”

Section: Oxidative Stress Associated With Organic Compounds—implicmentioning

confidence: 99%

The Role of Oxidative Stress in Carcinogenesis Induced by Metals and Xenobiotics

Henkler

Brinkmann

Luch

2010

Cancers

159

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In addition to a wide range of adverse effects on human health, toxic metals such as cadmium, arsenic and nickel can also promote carcinogenesis. The toxicological properties of these metals are partly related to generation of reactive oxygen species (ROS) that can induce DNA damage and trigger redox-dependent transcription factors. The precise mechanisms that induce oxidative stress are not fully understood. Further, it is not yet known whether chronic exposures to low doses of arsenic, cadmium or other metals are sufficient to induce mutations in vivo, leading to DNA repair responses and/or tumorigenesis. Oxidative stress can also be induced by environmental xenobiotics, when certain metabolites are generated that lead to the continuous release of superoxide, as long as the capacity to reduce the resulting dions (quinones) into hydroquinones is maintained. However, the specific significance of superoxide-dependent pathways to carcinogenesis is often difficult to address, because formation of DNA adducts by mutagenic metabolites can occur in parallel. Here, we will review both mechanisms and toxicological consequences of oxidative stress triggered by metals and dietary or environmental pollutants in general. Besides causing DNA damage, ROS may further induce multiple intracellular signaling pathways, notably NF-κB, JNK/SAPK/p38, as well as Erk/MAPK. These signaling routes can lead to transcriptional induction of target genes that could promote proliferation or confer apoptosis resistance to exposed cells. The significance of these additional modes depends on tissue, cell-type and is often masked by alternate oncogenic mechanisms being activated in parallel.

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Cited by 33 publications

References 18 publications

Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

Role of the Aryl Hydrocarbon Receptor in Environmentally Induced Skin Aging and Skin Carcinogenesis

The Role of Oxidative Stress in Carcinogenesis Induced by Metals and Xenobiotics

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