title: Quartz exposure of the rat lung leads to a linear dose response in inflammation but not in oxidative DNA damage and mutagenicity.
abstract: Exposure to quartz and high concentrations of other poorly soluble particles can lead to the development of lung tumors in the rat. The mechanisms involved in particle-induced carcinogenesis seem to include inflammation-associated production of reactive oxygen species (ROS) and DNA damage. ROS induce 8-oxoguanine (8-oxoGua) and a panel of other oxidation products in DNA. In proliferating cells such DNA lesions can lead to various types of mutations, which might be critical for cancer-related genes with respect to tumor formation. Quartz is known to mediate the induction of 8-oxoGua in the nuclear DNA of lung cells when applied to the lung of rats. We have investigated the time- and dose-dependent biologic effects of quartz and, as a control, corundum, on cell proliferation and various pulmonary inflammation and toxicity markers in rat bronchoalveolar lavage fluid (BALF); on the induction of 8-oxoGua in the DNA of rat lung cells; and on the cellular levels of p53 wild-type and p53 mutant (mut) protein. Rats were exposed by intratracheal instillation to various amounts of quartz (0.3, 1.5, or 7.5 mg/rat) or corundum (0.3, 1.5, or 7.5 mg/rat) and measured at Days 7, 21, and 90 after exposure. Corundum had no adverse effects except a slight elevation of 8-oxoGua at a dose of 7.5 mg/rat. However, significant changes in the BALF were detected at all quartz doses. 8-oxoGua was significantly increased only at 1.5 and 7.5 mg quartz/rat. The amount of cells with detectable p53 wild-type protein levels was increased at 1.5 and 7.5 mg quartz/rat at 7 and 21 d. Elevated amounts of cells with enhanced p53 mut protein levels were measured at all time points after instillation of 7.5 mg quartz/rat.
authors: Institute of Hygiene and Occupational Medicine, University of Essen Medical School, Germany.
authors: F
authors: F
authors: Seiler
authors: B
authors: B
authors: Rehn
authors: S
authors: S
authors: Rehn
authors: M
authors: M
authors: Hermann
authors: J
authors: J
authors: Bruch
mesh_terms: D000537:Aluminum Oxide / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D009153:Mutagens / Q000633:toxicity; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D011506:Proteins / Q000032:analysis; D011791:Quartz / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D019394:Ki-67 Antigen; D009153:Mutagens; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D011791:Quartz; C024829:8-hydroxyguanine; D006147:Guanine; D000537:Aluminum Oxide