Mechanistic in vitro studies: What they have told us about carcinogenic properties of elongated mineral particles (EMPs)

Toxicology and Applied Pharmacology
Brooke Mossman

Abstract

In vitro studies using target and effecter cells of mineral-induced cancers have been critical in determining the mechanisms of pathogenesis as well as the properties of elongated mineral particles (EMPs) important in eliciting these responses. Historically, in vitro models of 'mutagenesis' and immortalized cell lines were first used to test the theory that EMPs were mutagenic to cells, and 'genotoxicity', as defined as damage to DNA often culminating in cell death, was observed in a dose-dependent fashion as responses of many cell types to a number of EMPs. As two-stage and multi-step models of cancer development emerged in the 1970s and 1980s, differentiated 3D organ cultures and monolayers of lung epithelial and mesothelial cells were used to probe the mechanisms of cancer development. These studies demonstrated a spectrum of pre-neoplastic changes, including hyperplasia and squamous metaplasia, in response to long (>5 μm in length) needlelike EMPs whereas long, curly chrysotile fibers caused acute cytotoxicity. Shorter fibers of many types were taken up by cells and encompassed in phagolysosomes. Comparative studies using chemical carcinogens showed that chemical agents interacted directly with DNA whereas long EMPs appeare...Continue Reading

Citations

Feb 12, 2020·Health Expectations : an International Journal of Public Participation in Health Care and Health Policy·Kathryn BerzinsAbigail Albutt
Feb 4, 2021·Risk Analysis : an Official Publication of the Society for Risk Analysis·Linda D DellKenneth A Mundt
Mar 7, 2021·Toxicology·Alessandro F GualtieriDario Di Giuseppe
Jun 2, 2021·Critical Reviews in Toxicology·A Michael IerardiShannon Gaffney

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