Establishing a role for environmental toxicant exposure induced epigenetic remodeling in malignant transformation

Humphrey, Kristen; Pandey, Sumali; Martin, J. W.; Hagoel, Tamara J; Grand’Maison, Anne; Ohm, Joyce E.

doi:10.1016/j.semcancer.2018.11.002

Cited by 13 publications

(10 citation statements)

References 126 publications

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“…The network of effects and interactions between different chemicals in human exposome affecting varied physiological processes diverges from the classic reductionist views of one chemical-one target [44]. Analysis of causal relations in these complex settings is still a challenge [40], but advances in toxicology from multi-level (molecular to environmental) and systems biology approaches have been refining carcinogen classes, dose-response relationships and toxicity mechanisms especially relevant for chronic illness [46][47][48].…”

Section: Complexity Of the Carcinogenic Processes Related To Environm...mentioning

confidence: 99%

“…Multiple data show relevant associations between cancer incidence and exposure to various environmental toxicants, most notably heavy metals and pesticides [39,40]. Exposure to metals, including arsenic (As), cadmium (Cd), hexavalent chromium (Cr(VI)) and nickel (Ni), induce cell transformation and have been linked to different types of cancer in humans [39,41].…”

Section: Environmental Carcinogensmentioning

confidence: 99%

“…While the genotoxicity of (single) chemicals keeps being extensively probed, other phenomena are increasingly established as contributing to carcinogenesis or mutagenesis, namely inflammation, infections, endocrine disruption, epigenetic changes, immune dysfunction or redox imbalance [12,39,40,44,[49][50][51] (Fig. 2).…”

Section: Complexity Of the Carcinogenic Processes Related To Environm...mentioning

confidence: 99%

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Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Lagoa

Marques‐da‐Silva

Diniz

et al. 2022

Seminars in Cancer Biology

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Section: Complexity Of the Carcinogenic Processes Related To Environm...mentioning

confidence: 99%

Section: Environmental Carcinogensmentioning

confidence: 99%

Section: Complexity Of the Carcinogenic Processes Related To Environm...mentioning

confidence: 99%

See 1 more Smart Citation

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Lagoa

Marques‐da‐Silva

Diniz

et al. 2022

Seminars in Cancer Biology

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“…Exposure to TCDD from Agent Orange is believed to be an immunotoxin and the probable cause of several types of cancer in Vietnam veterans based on its clear carcinogenicity in experimental animal models [123]. One key mechanism proposed for TCDD carcinogenicity is epigenetic remodeling [124]. Supporting this view, exposure to dioxins or dioxin-like compounds has been associated with CNS developmental abnormalities in zebrafish and epigenetic modifications are well known to be particularly important during neuronal development [125].…”

Section: Persistent Organic Pollutants (Pops): Pcbs and Dioxinsmentioning

confidence: 99%

A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk

et al. 2022

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Multiple studies indicate that United States veterans have an increased risk of developing amyotrophic lateral sclerosis (ALS) compared to civilians. However, the responsible etiological factors are unknown. In the general population, specific occupational (e.g. truck drivers, airline pilots) and environmental exposures (e.g. metals, pesticides) are associated with an increased ALS risk. As such, the increased prevalence of ALS in veterans strongly suggests that there are exposures experienced by military personnel that are disproportionate to civilians. During service, veterans may encounter numerous neurotoxic exposures (e.g. burn pits, engine exhaust, firing ranges). So far, however, there is a paucity of studies investigating environmental factors contributing to ALS in veterans and even fewer assessing their exposure using biomarkers. Herein, we discuss ALS pathogenesis in relation to a series of persistent neurotoxicants (often emitted as mixtures) including: chemical elements, nanoparticles and lipophilic toxicants such as dioxins, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. We propose these toxicants should be directly measured in veteran central nervous system tissue, where they may have accumulated for decades. Specific toxicants (or mixtures thereof) may accelerate ALS development following a multistep hypothesis or act synergistically with other service-linked exposures (e.g. head trauma/concussions). Such possibilities could explain the lower age of onset observed in veterans compared to civilians. Identifying high-risk exposures within vulnerable populations is key to understanding ALS etiopathogenesis and is urgently needed to act upon modifiable risk factors for military personnel who deserve enhanced protection during their years of service, not only for their short-term, but also long-term health.

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“…The exposure to environmental toxicants has been a worldwide issue but it is still challenging to extrapolate data to human population. According to Humphrey et al (2019), the main limitations of this extrapolation are the variability of exposure routes to environmental chemicals, the complexity of the mixtures, biotransformation, metabolic processing, and human lifestyle. In this sense, the relationship between many toxicants and cancer progression remains poorly studied.…”

Section: ) Introductionmentioning

confidence: 99%

BDE-209 Becreases the Efficacy of Dacarbazine Treatment for Melanoma in C57BL/6 Mice

Manuitt-Brito

Souza

Neto

et al. 2021

Preprint

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Humans are widely exposed to environmental chemical toxicants potentially related to disease susceptibility. Polybrominated diphenyl ethers (PBDEs) present a proven risk associated with cancer, but no studies are related with the tumor progression. The decabromodiphenyl ether (BDE-209) is a flame-retardant detected in human plasma, breast milk and umbilical cord. Melanoma is a skin cancer with high metastatic potential and poor response to therapies. The use of alkylating agents such as dacarbazine is still a common protocol for the treatment of melanoma, mainly in Brazilian Public Health Care System. Recently, we reported the role of BDE-209 on the incidence of melanoma metastasis in different organs of mice after inoculation of B16-F10 cells. In the current study, we describe the effects of BDE-209 on dacarbazine treatment for melanoma. Adult male and female C57BL6 mice were exposed to BDE-209 for 45 days, inoculated with B16-F10 cells and treated with dacarbazine for 21 days (five doses of 40 mg.kg− 1). At 66th day, the animals were euthanized, and the blood, lung, liver, kidney and brain were sampled for hematological, biochemical and metastasis counting analyses. The results showed a decrease of lung metastases in animals treated with dacarbazine and a significant increase in mice previously exposed to BDE-209. Foremost, BDE-209 impaired dacarbazine treatment. These findings demonstrate the effect of BDE-209 and the decreased efficacy of dacarbazine treatment, favoring cancer progression and affecting the disease prognosis.

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Establishing a role for environmental toxicant exposure induced epigenetic remodeling in malignant transformation

Cited by 13 publications

References 126 publications

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk

BDE-209 Becreases the Efficacy of Dacarbazine Treatment for Melanoma in C57BL/6 Mice

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