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Reconstituted 2D Cell and Tissue Models
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Nicole Schneider-Daum, Patrick Carius, Justus C. Horstmann, Claus-Michael Lehr
The pulmonary acinus comprises the alveolar ducts that terminate in two or three alveolar sacs each. One alveolar sac consists of many alveoli, whereby one alveolus forms the functional unit of gas exchange. Each alveolus in turn is lined by cells of the alveolar epithelium. The expansion of the respiratory airways makes it possible that the surface area covered by the alveolar epithelium (~100 m2) amounts to more than 99% of the internal surface area of the lungs (Gehr et al. 1978; Mercer et al. 1994). The alveolar epithelium is formed by AT I and AT II pneumocytes that separate the air-filled respiratory lumen from the bloodstream, thereby forming the “air-blood barrier.” The flat AT I cells have a share of 8% of all lung cells, with one AT I cell covering a vast area of ~5000 µm² on average, comprising 95%–98% of the internal surface area (Crapo et al. 1982).
Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Daniel Krewski, Jerry M. Rice, Michael Bird, Brittany Milton, Brian Collins, Pascale Lajoie, Mélissa Billard, Yann Grosse, Vincent J. Cogliano, Jane C. Caldwell, Ivan I. Rusyn, Christopher J. Portier, Ronald L. Melnick, Robert A. Baan, Julian Little, Jan M. Zielinski
Although PeCDF provided sufficient evidence of carcinogenicity in animals, no animal site was identified. PeCDF was tested by the United States National Toxicology Program in a 2-year animal bioassay (female rats only) with exposure by oral gavage (National Toxicology Program 2006). There was some evidence of carcinogenic activity of PeCDF, based upon elevated incidences of hepatocellular adenoma and cholangiocarcinoma of the liver and gingival squamous cell carcinoma of the oral mucosa. The occurrence of cystic keratinizing epithelioma of the lung, neoplasms of the pancreatic acinus, and carcinoma of the uterus may have been related to administration of PeCDF. There were also three rat experiments with PeCDF in combination with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and N-nitrosodiethylamine (NDEA), where increased tumor multiplicity was found in each case (IARC 2012c). These observations led to the conclusion that there is sufficient evidence for carcinogenicity of PeCDF in animals, although there was no specific organ site that might be designated as responsible for this sufficient evidence. Because of the absence of a specific tumor site in animals, PeCDF is not included in the concordance analyses.