Role of inflammation in chemical-induced lung cancer

Emmendoerffer, Andreas; Hecht, Matthias; Boeker, Tanja; Mueller, M; Heinrich, Uwe

doi:10.1016/s0378-4274(99)00285-4

Cited by 52 publications

(34 citation statements)

References 26 publications

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“…Another relevant feature of this model is the intimate link between chronic inflammation and carcinogenesis, similar to human lung cancer. [29][30][31] The heterotypic interactions taking place between epithelial and immune cells have been shown to play an important role in tumor initiation, maintenance and development. 32 Another interesting finding in this model was the appearance of the EMT, a common signature in many types of cancer.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelialmesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood. We have used a rat model for multistep lung carcinogenesis to study the status of adherens and tight junction proteins and mesenchymal markers during EMT. After silica-induced chronic inflammation, rats sequentially develop epithelial hyperplasia, preneoplastic lesions, and tumors such as adenocarcinomas and squamous cell carcinomas. In comparison with normal and hyperplastic bronchiolar epithelium and with hyperplastic alveolar type II cells, the expression levels of E-cadherin, a-catenin and b-catenin were significantly reduced in adenomatoid preneoplastic lesions and in late tumors. The loss of E-cadherin in tumors was associated with its promoter hypermethylation. a-and b-catenin dysregulation lead to cytoplasmic accumulation in some carcinomas. No nuclear b-catenin localization was found at any stage of any preneoplastic or neoplastic lesion. Zonula occludens protein-1 was markedly decreased in 66% of adenocarcinomas and in 100% squamous cell carcinomas. The mesenchymal-associated proteins N-cadherin and vimentin were analyzed as markers for EMT. N-cadherin was de novo expressed in 32% of adenocarcinomas and 33% of squamous cell carcinomas. Vimentin-positive tumor cells were found in 35% of adenocarcinomas and 88% of squamous cell carcinomas. Mesenchymal markers were absent in precursor lesions, both hyperplastic and adenomatoid. The present results show that silica-induced rat lung carcinogenesis is a good model to study EMT in vivo, and also provide in vivo evidence suggesting that the changes in cell-cell adhesion molecules are an early event in lung carcinogenesis, while EMT occurs at a later stage.

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Section: Discussionmentioning

confidence: 99%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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“…A number of endocrine disruptor assays have been developed for the respective screening programs, and some of them have even been validated and accepted at OECD level. Mode of action based tests also are available for many other mechanisms, or they can be easily adapted from tests designed for other purposes; for example, inflammation represents another non-genotoxic mechanism (Emmendoerffer et al, 2000;Ohshima et al, The cancer bioassay is a "one size fits all" assay and is, by definition, problematic, as a testing assay can be either specific or sensitive -but not both. We believe that an alternative to the bioassay, in the form of an integrated testing strategy (ITS) using animal-free tests -which is then subjected to probabilistic risk assessment -would provide better information on the carcinogenic risks of new and existing chemicals to regulatory agencies and the public.…”

Section: Specific Considerations For Non-genotoxic Carcinogensmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

201

162

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“…Kjemokiner som interleukin-8 (IL-8) er sentrale i rekruttering av nøytrofile inflammasjonsceller til skadestedet (35). Betennelsesreaksjoner kan også ha betydning for utvikling av lungekreft på grunn av økt dannelse av reaktive oksygenforbindelser og økt proliferasjon (37). Imidlertid synes en direkte reaksjon mellom komponenter i svevestøvet og genmaterialet å vaere av størst betydning for kreftutvikling.…”

Section: Luftveissystemetunclassified

Helseeffekter av byluftpartikler

Refsnes¹,

Låg²,

Hetland³

et al. 2009

Nor J Epidemiol

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SAMMENDRAGSvevestøv i byluft består av forbrenningspartikler og mineralpartikler med svaert forskjellige størrelser og kjemiske egenskaper. Svevestøvet kan deles inn i størrelsesfraksjoner som PM 10 (PM £ 10 mm), PM 2,5 (PM £ 2,5 mm) og PM 0,1 (PM £ 0,1 mm). Nyere befolkningsstudier viser en assosiasjon mellom økning i dødelighet og sykelighet (pga. lunge-og hjertekarsykdommer) og kortvarige økninger i svevestøvskonsentrasjoner i byluft. Den relative risikoen (RR) er rundt 1,005 ved en økning av PM 10 på 10 mg/m 3 , uten noen observert terskelverdi, selv ved nivåer under 10 mg/m 3 . Kronisk eksponering for svevestøv er mindre undersøkt, men årelang eksponering for PM 2,5 er assosiert med en RR som er omlag 10 ganger større enn ved korttidseksponering. Befolkningsstudiene indikerer at enkelte grupper synes å vaere spesielt følsomme (lungesyke, hjertesyke og barn). Hos frivillige individer i kammer-og feltstudier, fant man effekter både i luftveiene og i hjerte-karsystemet ved konsentrasjoner av svevestøv (PM 2,5 /PM 10 : 100-200 mg/m 3 ) som kan forekomme i episoder med økt luftforurensning. Dyreforsøk med høyere konsentrasjoner ga kraftigere responser. De eksperimentelle studiene understøtter befolkningsstudiene i at byluftpartikler representerer et helseproblem. Både befolkningsstudiene og eksperimentelle studier indikerer at enkelte individer er mer sårbare enn andre. Ved lave til middels konsentrasjoner av byluftpartikler synes det å foreligge en diskrepans mellom disse studietypene som kan skyldes at de mest sårbare individene ikke er inkludert i eksperimentelle forsøk. Studier med mennesker, dyr og celler viser at fysisk/kjemiske egenskaper ved partiklene (størrelse, innhold av metaller, organiske forbindelser, endotoksiner etc.) er sentrale for de observerte effektene av svevestøvet. Mer kunnskap både om helseeffekter ved lave konsentrasjoner, samt egenskaper ved partikler, er nødvendig.Refsnes M, Låg M, Hetland RB, Schwarze PE. Ambient air particles and adverse health effects.Nor J Epidemiol 2004; 14 (2): 145-154.

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Role of inflammation in chemical-induced lung cancer

Cited by 52 publications

References 26 publications

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Helseeffekter av byluftpartikler

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