Molecular Mechanisms of Chromium-Induced Carcinogenesis

Browning, Cynthia L.; Speer, Rachel M.; Wise, John Pierce

doi:10.1007/978-3-319-55448-8_7

Cited by 6 publications

(2 citation statements)

References 108 publications

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“…The human studies in which epigenetic alterations were measured (DNA methylation or histone methylation in blood) were specific to inhalational occupational exposure. Although the involvement of epigenetic mechanisms in Cr(VI)-induced cancer has been reported, particularly lung cancer in humans occupationally exposed via inhalation ( Browning et al , 2017 ; Chen et al , 2019 ; Rager et al , 2019 ), the potential relevance or involvement of the same or similar epigenetic alterations in Cr(VI)-induced intestinal cancer is not clear.…”

Section: Resultsmentioning

confidence: 99%

Assessment of Mechanistic Data for Hexavalent Chromium-Induced Rodent Intestinal Cancer Using the Key Characteristics of Carcinogens

Chappell

Wikoff

Thompson

2021

Toxicological Sciences

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Oral exposure to hexavalent chromium (Cr[VI]) induces intestinal tumors in mice. Mutagenic and nonmutagenic modes of action (MOAs) have been accepted by different regulatory bodies globally, the latter involving cytotoxicity-induced regenerative cell proliferation. However, concerns persist that all possible MOAs have not been fully considered. To address the potential for alternative MOAs, mechanistic data not represented in the existing two MOAs were evaluated. Relevant data were identified and organized by key characteristics of carcinogens (KCCs); literature related to epigenetics, immunosuppression, receptor-mediated effects, and immortalization were reviewed to identify potential key events associated with an alternative MOA. Over 200 references were screened for these four KCCs and further prioritized based on relevance to the research objective (ie, in vivo, oral exposure, gastrointestinal tissue). Minimal data were available specific to the intestine for these KCCs, and there was no evidence of any underlying mechanisms or key events that are not already represented in the two proposed MOAs. For example, while epigenetic dysregulation of DNA repair genes has been demonstrated, epigenetic effects were not measured in intestinal tissue, and it has been shown that Cr(VI) does not cause DNA damage in intestinal tissue. High-throughput screening data related to the KCCs were also evaluated, with activity generally limited to the two recognized MOAs. Collectively, no plausible alternative MOAs (or key events) were identified in addition to those previously proposed for Cr(VI) small intestine tumors.

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Section: Resultsmentioning

confidence: 99%

Assessment of Mechanistic Data for Hexavalent Chromium-Induced Rodent Intestinal Cancer Using the Key Characteristics of Carcinogens

Chappell

Wikoff

Thompson

2021

Toxicological Sciences

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“…Although the carcinogenic mechanism of Cr exposure is unclear, genomic instability and epigenetic modification have been identified during molecular processes linked to cancer ( Browning et al, 2017 ; Rager et al, 2019 ). In addition, in vivo Cr-related data illustrated genotoxicity and mutagenicity results have mostly been negative, and the mutagenic is not the main cause of Cr (VI)-induced cancer ( Proctor et al, 2014 ; Browning et al, 2017 ). Therefore, epigenetic modification, especially DNA methylation, may play a vital role in pathogenesis mechanism of Cr (VI) ( Feng et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Association of environmental exposure to chromium with differential DNA methylation: An epigenome-wide study

Zhao

et al. 2023

Front. Genet.

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Introduction: Previous studies have reported that chromium (Cr)-induced epigenetic alterations and DNA methylation play a vital role in the pathogenesis of diseases induced by chromium exposure. Epigenomic analyses have been limited and mainly focused on occupational chromium exposure; their findings are not generalizable to populations with environmental Cr exposure.Methods: We identified the differential methylation of genes and regions to elucidate the mechanisms of toxicity related to environmental chromium exposure. DNA methylation was measured in blood samples collected from individuals in Cr-contaminated (n = 10) and unexposed areas (n = 10) by using the Illumina Infinium HumanMethylation850K array. To evaluate the relationship between chromium levels in urine and CpG methylation at 850 thousand sites, we investigated differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by using linear models and DMRcate method, respectively. The model was adjusted for biologically relevant variables and estimated cell-type compositions.Results: At the epigenome-wide level, we identified five CpGs [cg20690919 (pFDR =0.006), cg00704664 (pFDR =0.024), cg10809143 (pFDR =0.043), cg27057652 (pFDR =0.047), cg05390480 (pFDR =0.024)] and one DMR (chr17: 19,648,718-19,648,972), annotated to ALDH3A1 genes (p < 0.05) as being significantly associated with log2 transformed urinary chromium levels.Discussion: Environmental chromium exposure is associated with DNA methylation, and the significant DMPs and DMR being annotated to cause DNA damage and genomic instability were found in this work. Research involving larger samples is required to further explore the epigenetic effect of environmental chromium exposure on health outcomes through DNA methylation.

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Systemic Essential Metal and Metalloid Levels in Patients with Benign Breast Disease and Breast Cancer

Skalny

Sekacheva

Aschner

et al. 2022

Biol Trace Elem Res

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Molecular Mechanisms of Chromium-Induced Carcinogenesis

Cited by 6 publications

References 108 publications

Assessment of Mechanistic Data for Hexavalent Chromium-Induced Rodent Intestinal Cancer Using the Key Characteristics of Carcinogens

Assessment of Mechanistic Data for Hexavalent Chromium-Induced Rodent Intestinal Cancer Using the Key Characteristics of Carcinogens

Association of environmental exposure to chromium with differential DNA methylation: An epigenome-wide study

Systemic Essential Metal and Metalloid Levels in Patients with Benign Breast Disease and Breast Cancer

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