Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats.
Inhaled fibres with certain physico-chemical properties are known to induce mesothelioma in humans. The induction of reactive oxygen (ROS) or nitrogen species (RNS) have been suggested as molecular mechanism of fibre induced carcinogenesis. In earlier studies we were able to demonstrate that crocidolite asbestos in vivo induces mutations in transgenic rats with a specific molecular spectrum that indicates the involvement of 8-hydroxydeoxyguanosine (8-OHdG) as pre-mutagenic adduct. 8-OHdG may be induced by primary (direct) and/or secondary (cellular mediated) mechanisms. Therefore, the induction of 8-OHdG as well as the inflammatory response of animals treated with fibre samples significantly differing in their physico-chemical characteristics was investigated. As appropriate system to study mesothelioma carcinogenesis, intraperitoneal injection in rats was used with samples of UICC crocidolite, crocidolite with reduced iron content, and a vitreous fibre (MMVF 11). Equal numbers of carcinogenic fibres from each sample revealed significant comparable increases in 8-OHdG induction. Parameters of inflammation (percentage of macrophages and TNF-alpha secretion) correlated significantly with the induction of 8-OHdG, 10 weeks after treatment.
Schürkes
Claudia
C
Institut für umweltmedizinische Forschung, an der Heinrich-Heine-Universität Düsseldorf gGmbH, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Brock
Winfried
W
Abel
Josef
J
Unfried
Klaus
K
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000818:Animals; D017638:Asbestos, Crocidolite / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007274:Injections, Intraperitoneal; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D019016:Mineral Fibers / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D007507:Therapeutic Irrigation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019016:Mineral Fibers; D014409:Tumor Necrosis Factor-alpha; D017638:Asbestos, Crocidolite; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA