Strong nasal carcinogenicity and genotoxicity of 1-nitroso-4-methylpiperazine after low dose inhalation in rats

• Verfasst von: Klein, Reinhold G. [VerfasserIn]
• Verfasst von: Schmezer, Peter [VerfasserIn]
• Verfasst von: Spiegelhalder, Bertold [VerfasserIn]
• Verfasst von: Bartsch, Helmut [VerfasserIn]
• Titel: Strong nasal carcinogenicity and genotoxicity of 1-nitroso-4-methylpiperazine after low dose inhalation in rats
• Verf.angabe: R.G. Klein, P. Schmezer, R. Hermann, P. Waas, B. Spiegelhalder and H. Bartsch
• E-Jahr: 1999
• Jahr: 01 August 1999
• Umfang: 3 S.
• Fussnoten: Gesehen am 02.02.2021
• Titel Quelle: Enthalten in: Carcinogenesis
• Ort Quelle: Oxford : Oxford Univ. Press, 1980
• Jahr Quelle: 1999
• Band/Heft Quelle: 20(1999), 8, Seite 1629-1632
• ISSN Quelle: 1460-2180
• DOI: doi:10.1093/carcin/20.8.1629
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1746723807

Abstract

Sprague-Dawley rats were exposed by inhalation to 1-nitroso-4-methylpiperazine (NMPz) vapor at 2.4 p.p.m. for 15 h/day for 74 days over a 7.5 month period. After a dose of 1.1 mg/day NMPz (total dose 340 mg/kg body wt) 10/10 animals developed tumors of the nasal cavity, mostly invasive muco-epidermoidal carcinomas; no such tumors were observed in sham-exposed controls. This high tumor yield was seen at an 80 times lower dose and a shorter latency period when compared with rat carcinogenicity studies reported earlier. The single cell microgel electrophoresis (Comet) assay was used to determine genotoxicity in target tissues. Short-term in vitro exposure of rat and human nasal epithelial tissues to NMPz caused genotoxic effects in cells of both species. Short-term in vivo exposure of rats to NMPz vapor for 1 h induced DNA damage in nasal epithelial cells. Our results revealed NMPz as a potent genotoxic nitrosamine in rat and human nasal cells, the carcinogenicity of inhaled NMPz vapor in rats being remarkably higher as compared with oral uptake.