CL:0000066 CL epithelial cell D010212 MESH papilloma D002277 MESH Carcinoma GO:0008219 GO cell death GO:0006954 GO inflammatory response GO:0008283 GO cell proliferation MP:0005493 MP stomach epithelial hyperplasia 1 WIKI increased Propylene oxide 2016-11-29T18:42:27 2016-11-29T18:42:27 9606 NCBI Homo sapiens 10090 NCBI Mus musculus 10116 NCBI Rattus norvegicus Increase, Cytotoxicity (epithelial cells) Cellular <p>This key event is often associated with gavaged administration. </p> CL:0000066 CL epithelial cell AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:14 Increase, Inflammation Cellular <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Inflammation is complex to define.&nbsp; </span></span></p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Villeneuve et al. (2018) analyzed the varied biological responses, provided guidance to simplify the &nbsp;process representing inflammation in adverse outcome pathways, and recommended 3 key steps: 1. Tissue resident cell activation 2. Increased Pro-inflammatory mediators 3. Leukocyte recruitment/activation.&nbsp; Tissue resident cell activation generally occurs when healthy tissue is exposed to a stressor, or when damage occurs, initiating a signal response of pro-inflammatory mediators (ex. cytokines).&nbsp; Pro-inflammatory mediators result in the production of lipids and proteins, signaling, and initiate leukocyte recruitment/activation.&nbsp; Leukocyte recruitment/activation initiate inflammation and other morphological changes.&nbsp; </span></span></p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Some empirical research studies that illustrate inflammation pathways:</span></span></p> <ul> <li><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">A review of inflammation caused by microplastics in mammals (Wright and Kelly, 2017).&nbsp; Inflammation and immune responses are caused by irritation via microplastics inhalation.</span></span></li> <li><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Increased inflammatory interleukin gene expression in lab mice brains with damaged hypoglossal nerves (Gamo et al., 2008).&nbsp; Inflammatory genes interleukin-1beta and interleukin-6, and tumor necrosis factor-alpha levels were increased after physical injury.</span></span></li> <li><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Increased inflammation in the freshwater fish Danio rerio exposed to polystyrene microplastics (Lu et al., 2016).&nbsp; Oxidative stress indicator enzymes superoxide dismutase and catalase were increased in livers, along with histopathological changes in inflammation and necrosis, in response to accumulation of microplastics.</span></span></li> <li><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Inhibited inflammatory interleukin gene expression in guts and increased mucus production in guts in the freshwater fish Danio rerio exposed to polystyrene microplastics (Jin et al., 2018).&nbsp; Gene expression of tumor necrosis factor-alpha, interleukin-1alpha, interleukin-1beta, interferon, interleukin-6, interleukin-8, interleukin-10 were changed, with most genes showing statistically significant increases and a dose-response relationship, due to exposure to polystyrene microplastics.&nbsp; In additional, gut microbiota was altered.</span></span></li> <li><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Significant intestinal damage including intestinal fold disruption, enterocyte damage, broken tissue, and inflammation in the freshwater fish Danio rerio exposed to microplastics (Lei et al., 2018).&nbsp; Growth and reproductive effects were seen in addition to the histology observations, and associated with accumulation of microplastics.</span></span></li> </ul> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">In cancer, inflammation is a cascade of events created by the host in response to the spread of the cancer (Coussens and Werb, 2002). In response to an injury or the presence of cancer, the host heals itself through inflammation. Indeed, the activation and the migration of&nbsp; leukocytes (neutrophils, monocytes and eosinophils) to the wound induces the healing process. These inflammatory cells provide an extracellular matrix that forms upon which fibroblast and endothelial cells proliferate and migrate in order to recreate a normal environment. Damage to the epithelial layer initiate inflammatory reactions (Palmer et al. 2011).&nbsp; In cancer, this inflammatory state induces cell proliferation, increases the production of reactive oxygen species leading to oxidative DNA damage, and reduces DNA repair (Coussens and Werb, 2002).</span></span></p> <p>&nbsp;</p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Inflammation is generally detected in histopathological examination of organs (ex. liver, intestines) or in changes in gene expression (ex. interleukins).&nbsp; Activation of the innate immune response and the release of various inflammatory cytokines can also be assessed (Flake and Morgan, 2017). </span></span></p> <p><span style="font-size:16px"><span style="font-family:&quot;Calibri&quot;,sans-serif">Taxonomic:&nbsp;appears to be present broadly, with representative studies focused on mammals (humans, lab mice, lab rats).</span></span></p> <p>&nbsp;</p> CL:0000255 CL eukaryotic cell High Unspecific High All life stages High High High <p><span style="font-size:16px">Flake, G.P., and&nbsp;Morgan, D.L. 2017. Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis. <em>Toxicology</em>, <em>388</em>, 40&ndash;47. <a href="https://doi.org/10.1016/j.tox.2016.10.013"><u>https://doi.org/10.1016/j.tox.2016.10.013</u></a></span></p> <p><span style="font-size:16px">Palmer, S.M., Flake, G.P., Kelly, F.L., Zhang, H.L., Nugent, J.L., Kirby, P.J., Zhang, H.L., Nugent, J.L., Kirby, P.J., Foley, J.F., Gwinn, W.M., and Morgan, D.L. 2011. Severe airway epithelial injury, aberrant repair and Bronchiolitis obliterans develops after diacetyl instillation in rats. <em>PLoS ONE</em>,&nbsp;<em>6</em>(3).&nbsp;<a href="https://doi.org/10.1371/journal.pone.0017644"><u>https://doi.org/10.1371/journal.pone.0017644</u></a></span></p> <p><span style="font-size:16px">Coussens L.M. and Werb Z. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7. doi: 10.1038/nature01322. PMID: 12490959; PMCID: PMC2803035.</span></p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Gamo, K., Kiryu-Seo, S., Konishi, H., Aoki, S., Matushima, K., Wada, K., and Kiyama, H.&nbsp; 2008.&nbsp; G-protein-coupled receptor screen reveals a role for chemokine recepteor CCR5 in suppressing microglial neurotoxicity.&nbsp; Journal of Neuroscience 28: 11980-11988.</span></span></p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif"><span style="color:black">Jin, Y., Xia, J., Pan, Z., Yang, J., Wang, W., and Fu, Z.&nbsp; 2018.&nbsp; Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.&nbsp; Environmental Pollution 235: 322-329.</span></span></span></p> <p><span style="font-size:16px"><span style="font-family:Calibri,sans-serif">Lei, L., Wu, S., Lu, S., Liu, M., Song, Y., Fu, Z., Shi, H., Raley-Susman, K.M., and He, D.&nbsp; 2018.&nbsp; Microplastic particles cause intestinal damage and other adverse effects in zebrafish Danio rerio and nematode Caenorhabditis elegans.&nbsp; Science of the Total Environment 619-620: 1-8.</span></span></p> AOPWiki 2016-11-29T18:41:23 2023-08-10T14:43:51 Increase, Regenerative cell proliferation (forestomach epithelial cells) Cellular UBERON:0008827 UBERON murine forestomach AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:14 Increase, Hyperplasia (forestomach epithelial cells) Cellular UBERON:0008827 UBERON murine forestomach AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:14 Increase, Papillomas/carcinomas (squamous cells) Cellular CL:0000076 CL squamous epithelial cell AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:12 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4313625120> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b431363e990> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 <p>Sustained regenerative cell proliferation directly leads to hyperplasia. </p> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4313650640> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b431366a6f8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 Epithelial cytotoxicity- forestomach tumor Agnes Aggy <p>Cancer AOP group. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (wood.charles@epa.gov)</p> BY-SA 1.29 1.0 <p>This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.</p> adjacent Not Specified Not Specified adjacent Not Specified Not Specified adjacent Not Specified Not Specified adjacent Not Specified Not Specified Not Specified Male Not Specified Female Not Specified Not Specified <p>Proctor, D. M., Gatto, N. M., Hong, S. J., &amp; Allamneni, K. P. (2007). Mode-of-action framework for evaluating the relevance of rodent forestomach tumors in cancer risk assessment. Toxicol Sci, 98(2), 313-326. doi: 10.1093/toxsci/kfm075</p> AOPWiki 2016-11-29T18:41:16 2023-09-25T16:26:50