Key characteristics of 86 agents known to cause cancer in humans

Krewski, Daniel; Bird, Michael G.; Al-Zoughool, Mustafa; Birkett, Nicholas; Billard, Mélissa; Milton, Brittany; Rice, Jerry M.; Grosse, Yann; Cogliano, Vincent; Hill, Mark A.; Baan, R.A.; Little, Julian; Zielinski, Jan M.

doi:10.1080/10937404.2019.1643536

Cited by 42 publications

(33 citation statements)

References 40 publications

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“…On the basis of this classification, environmental contaminants represent one of the main contributors to tumor initiation, as abundantly documented by the increasing number of research studies during the past decade [ 36 ]. The list of chemical agents catalogued as carcinogenic includes the different conformers of hexachlorocyclohexane, among which stands out the well-known pesticide Lindane (γ-HCH) [ 37 ]. The problems connected with the extensive use of Lindane for agricultural purposes have drawn the attention of the scientific community, but this is just the tip of the iceberg: the industrial synthesis of Lindane generated large quantities of undesired isomers that constitute a significant source of contamination [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

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Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

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Section: Discussionmentioning

confidence: 99%

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

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“…Since the 1970s the International Agency for Research for Cancer (IARC) has screened over 1000 agents which exhibited a cancer risk to humans ( Krewski et al, 2019 ) . Over 100 carcinogenic agents can be divided into six general categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations ( Krewski, Rice, et al, 2019 ). Carcinogens including nitrosamines and aflatoxins can initiate or stimulate tumor growth and metastasis via multiple mechanisms including inflammation ( Shi, Godschalk, & van Schooten, 2017 ; Smith et al, 2016 ).…”

Section: Carcinogens and Inflammationmentioning

confidence: 99%

“…Carcinogens may not directly be genotoxic but cause DNA damage by stimulating inflammation. Chronic inflammation triggers oxidative stress via the release of pro-inflammatory cytokines and stimulation of cell proliferation, leading to DNA damage ( Krewski, Bird, et al, 2019 ). Heavy metals such as arsenic, aluminum, nickel, cadmium, chromium, cobalt, palladium, and titanium induce severe damage triggering pro-inflammatory cytokines and oxidative stress ( Jomova & Valko, 2011 ; Magrone, Russo, & Jirillo, 2019 ).…”

Section: Carcinogens and Inflammationmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

142

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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“…In a retrospective analysis of IARC Group-1 agents (Krewski et al, 2019), in vitro data were found to be widely used in the mechanistic evaluations of these agents, providing results that were generally consistent with in vivo data. With mechanistic considerations within the IARC Monographs Programme now focused on the ten key characteristics of human carcinogens, mechanistic data derived from NAMs may be expected to play a prominent role in defining the key characteristics in future evaluations.…”

mentioning

confidence: 64%

The Monographs Programme of the International Agency for Research on Cancer

Baan

Straif

2021

ALTEX

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Since the early 1970s, the Monographs published by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards. The Preamble to the IARC Monographs describes the objective and scope of the Programme, the scientific principles and procedures used in developing a Monograph, the types of evidence considered, and the scientific criteria that guide the evaluations. This article presents an overview of the historical development of the Preamble from the time it began to take shape in the late 1970s up to and including the most recent update in 2019. Over the years, the IARC Monographs Programme has taken account of scientific and procedural advances in identifying, reviewing, evaluating and integrating evidence to define causes of human cancer. Since the previous edition of the Preamble in 2006, the new developments include a stronger emphasis on mechanistic evidence based on key characteristics of carcinogens; greater consideration of exposure assessment methods in epidemiological studies; and integration of the streams of evidence on cancer in humans, cancer in experimental animals and mechanisms in reaching the overall evaluations. Thus, the Preamble now allows an evaluation process in the absence of data from animal studies, and the evidence on key characteristics of cancer may be contributed by new approach methodologies, thus potentially reducing or avoiding the use of experimental animals.

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Key characteristics of 86 agents known to cause cancer in humans

Cited by 42 publications

References 40 publications

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Carcinogenesis: Failure of resolution of inflammation?

The Monographs Programme of the International Agency for Research on Cancer

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