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dc.contributor.authorLuijten, Mirjam
dc.contributor.authorSpeksnijder, Ewoud N
dc.contributor.authorAlphen, Niels van
dc.contributor.authorWesterman, Anja
dc.contributor.authorHeisterkamp, Siem H
dc.contributor.authorBenthem, Jan van
dc.contributor.authorKreijl, Coen F van
dc.contributor.authorBeems, Rudolf B
dc.contributor.authorSteeg, Harrym van
dc.date.accessioned2007-01-10T13:07:54Z
dc.date.available2007-01-10T13:07:54Z
dc.date.issued2006-04-11
dc.identifier.citationMutat. Res. 2006, 596(1-2):143-50en
dc.identifier.issn0027-5107
dc.identifier.pmid16464479
dc.identifier.doi10.1016/j.mrfmmm.2005.12.011
dc.identifier.urihttp://hdl.handle.net/10029/7191
dc.description.abstractChronic use of phenacetin-containing analgesics has been associated with the development of renal cancer. To establish genotoxicity as a possible cause for the carcinogenic effect of phenacetin, we exposed wild type and DNA repair deficient Xpa-/- and Xpa-/-/Trp53+/- mice (further referred as Xpa and Xpa/p53 mice, respectively), carrying a reporter lacZ gene, to 0.75% (w/w) phenacetin mixed in feed. Xpa mice completely lack the nucleotide excision repair pathway, and as such they are sensitive to some classes of genotoxic compounds. Phenacetin exposure induced a significant increase of lacZ mutations in the kidney of both Xpa and Xpa/p53 mice. A minor response was found in liver, whereas no lacZ mutation induction was observed in the spleen of these animals. Interestingly, the observed phenacetin-induced mutant frequencies were higher in male than those found in female mice. This gender difference is probably due to a difference in metabolic rate. Phenacetin-induced mutations mainly consisted of point mutations rather than deletions. The mutational spectra in the kidney of treated WT and Xpa mice were quite similar. Taken together, these results demonstrate that the human carcinogen phenacetin acts as a weak genotoxic agent in an in vivo mouse model system.
dc.format.extent302884 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.titlePhenacetin acts as a weak genotoxic compound preferentially in the kidney of DNA repair deficient Xpa mice.en
dc.typeArticleen
dc.format.digYES
refterms.dateFOA2018-12-18T14:54:22Z
html.description.abstractChronic use of phenacetin-containing analgesics has been associated with the development of renal cancer. To establish genotoxicity as a possible cause for the carcinogenic effect of phenacetin, we exposed wild type and DNA repair deficient Xpa-/- and Xpa-/-/Trp53+/- mice (further referred as Xpa and Xpa/p53 mice, respectively), carrying a reporter lacZ gene, to 0.75% (w/w) phenacetin mixed in feed. Xpa mice completely lack the nucleotide excision repair pathway, and as such they are sensitive to some classes of genotoxic compounds. Phenacetin exposure induced a significant increase of lacZ mutations in the kidney of both Xpa and Xpa/p53 mice. A minor response was found in liver, whereas no lacZ mutation induction was observed in the spleen of these animals. Interestingly, the observed phenacetin-induced mutant frequencies were higher in male than those found in female mice. This gender difference is probably due to a difference in metabolic rate. Phenacetin-induced mutations mainly consisted of point mutations rather than deletions. The mutational spectra in the kidney of treated WT and Xpa mice were quite similar. Taken together, these results demonstrate that the human carcinogen phenacetin acts as a weak genotoxic agent in an in vivo mouse model system.


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