Transcriptomic analyses of livers from mice exposed to 1,4-dioxane for up to 90 days to assess potential mode(s) of action underlying liver tumor development

Chappell, Grace A.; Heintz, Melissa M.; Haws, Laurie C.

doi:10.1016/j.crtox.2021.01.003

Cited by 5 publications

(1 citation statement)

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“…MoA: The mechanism(s) of carcinogenicity of 1,4-dioxane has not been elucidated but is unlikely to involve genotoxicity. Studies suggested that hepatocarcinogenicity of 1,4-dioxane likely results from cytotoxicity followed by regenerative hyperplasia, in addition, mitogenic response was suggested as a key initiating event [ 815 , 834 , 835 , 836 , 837 ]. Such effects are threshold-dependent.…”

Section: Epigenetic Carcinogens or Carcinogens With Uncertain Mode Of...mentioning

confidence: 99%

Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk

Kobets

Smith

Williams

2022

Foods

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Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzo[a]pyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens.

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