Particles, inflammation and respiratory tract carcinogenesis.
Particle-induced carcinogenesis is a non-specific outcome of many different particles. It was the purpose of this study, (i) to comprehensively review some of the mechanisms through which particles and particle-associated carcinogens can cause mutagenic/carcinogenic effects, and (ii) to indicate how this affects risk assessment studies. Data are presented that demonstrate the crucial role of a chronic inflammatory response in mutagenic effects of both silica and carbon black particles on the HPRT gene in lung target cells. The concept of inflammation in particle-induced genotoxicity is put into the context of other mechanisms, such as the release of cytokines and reactive oxygen species. It is concluded that interpretation of rat inhalation studies should certainly include this concept.
Borm
P J
PJ
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.
Driscoll
K
K
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002244:Carbon / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D016296:Mutagenesis / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012142:Respiratory Tract Neoplasms / Q000209:etiology* / Q000473:pathology; D018570:Risk Assessment; D012822:Silicon Dioxide / Q000633:toxicity
D000393:Air Pollutants; D002273:Carcinogens; D016207:Cytokines; D017382:Reactive Oxygen Species; D002244:Carbon; D012822:Silicon Dioxide; D007041:Hypoxanthine Phosphoribosyltransferase