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A Molecular Look at “Spontaneous Mesotheliomas”

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.

#Asbestos

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About Kirk

Since becoming a lawyer in 1983, Kirk’s over 30 years of practice have focused on advising a wide range of corporations, associations, and individuals (as both plaintiffs and defendants) on both tort and commercial law issues centered around “mass torts.”

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