Influence of nucleotide excision repair on N-hydroxy-2-acetylaminofluorene-induced mutagenesis studied in λlacZ-transgenic mice
✍ Scribed by Anita F. W. Frijhoff; Cyrille A. M. Krul; Annemieke de Vries; Marco C. J. M. Kelders; Geert Weeda; Harry van Steeg; Robert A. Baan
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 73 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
To study the influence of nucleotide excision repair strain 40.6. The N-OH-AAF-induced mutation spec-(NER) on mutagenesis in vivo, ERCC1//0, XPA0/0, trum appeared to be significantly different from the and wild-type (ERCC1/// and XPA///, respec-spontaneous mutation spectrum: the former contively) llacZ-transgenic mice were treated i.p. with sisted of mainly (19/22) single bp substitutions N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and targeted at G, of which the majority (12/19) were lacZ mutant frequencies were determined in liver. G:C r T:A transversions, suggesting that N-(deoxy-No significant effect of the treatment on the mutant guanosin-8-yl)-2-aminofluorene [dG-C8-AF], the mafrequency in wild-type or ERCC1-heterozygous mice jor DNA adduct in N-OH-AAF-treated mice, is the was observed. The liver mutant frequency appeared premutagenic lesion. After analysis of 21 spontaneto be significantly increased in treated XPA0/0 ous mutants, only ten single bp substitutions targeted mice only. To distinguish N-OH-AAF-induced from at G were found, of which five were G:C r T:A spontaneous mutations, lacZ mutants derived from transversions. This study with XPA0/0 llacZtreated XPA0/0 mice were subjected to DNA-transgenic mice shows that one of the components sequence analysis and the spectrum obtained was of NER, that is, the XPA protein, suppresses mutacompared to that established for lacZ mutants in liver genesis in vivo.