Molecular toxicology studies continue to expand as scientists examine cells and systems to try to answer questions about "how and why." The investigations include asbestos-related diseases in particular. A new article from Toxicologic Pathology addresses "spontaneous mesotheliomas" in a strain of mice. The abstract is as follows:
Spontaneous Mesotheliomas in F344/N Rats Are Characterized by Dysregulation of Cellular Growth and Immune Function Pathways
Pamela E. Blackshear1
Arun R. Pandiri2
Thai-Vu T. Ton3
Natasha P. Clayton3
Keith R. Shockley4
Shyamal D. Peddada4
Kevin E. Gerrish5
Robert C. Sills3
Mark J. Hoenerhoff3
1Integrated Laboratory Systems, Inc., Research Triangle Park, North Carolina, USA
2Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina, USA
3Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
4Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
5Microarray Core, Toxicology and Pharmacology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
Mark J. Hoenerhoff, Investigative Pathology Group, Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, B350 Rall Building, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA; e-mail: hoenerhm@niehs.nih.gov.
Abstract
Aged male Fischer 344/N rats are prone to developing spontaneous peritoneal mesotheliomas that arise predominantly from the tunica vaginalis of the testes. A definitive cause for the predominance of this neoplasm in F344/N rats is unknown. Investigation of the molecular alterations that occur in spontaneous rat mesotheliomas may provide insight into their pathogenesis as well enable a better understanding regarding the mechanisms underlying chemically induced mesothelioma in rodents. Mesothelial cell function represents a complex interplay of pathways related to host defense mechanisms and maintenance of cellular homeostasis. Global gene expression profiles of spontaneous mesotheliomas from vehicle control male F344/N rats from 2-year National Toxicology Program carcinogenicity bioassays were analyzed to determine the molecular features of these tumors and elucidate tumor-specific gene expression profiles. The resulting gene expression pattern showed that spontaneous mesotheliomas are associated with upregulation of various growth factors, oncogenes, cytokines, pattern recognition response receptors, and pathogen-associated molecular patterns receptors, and the production of reactive oxygen and nitrogen species, as well as downregulation of apoptosis pathways. Alterations in these pathways in turn trigger molecular responses that stimulate cell proliferation and promote tumor survival and progression.
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