PMID: 11317337Apr 24, 2001Paper

Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats

Environmental and Molecular Mutagenesis
T ChenR H Heflich

Abstract

N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this study, transgenic Big Blue(R) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues. Male rats were given one, two, or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene, and lacI mutant frequencies were determined in the liver and spleen lymphocytes. At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10(-6) compared with 3.2 x 10(-6) in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6, 155.6, and 406.8 x 10(-6), respectively, compared with a control frequency of 25.7 x 10(-6); rats given four doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10(-6) compared with a control frequency of 20.4 x 10(-6). Additi...Continue Reading

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Citations

Sep 12, 2009·Critical Reviews in Toxicology·Annie M JarabekErrol Zeiger
Aug 27, 2010·Environmental and Molecular Mutagenesis·Barbara L ParsonsPage B McKinzie
Feb 9, 2017·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takehiko NohmiNaomi Toyoda-Hokaiwado
Oct 11, 2003·Mutation Research·Véronique ThybaudNobuhiro Yajima
Aug 6, 2005·Mutation Research·Iain B LambertGeorge R Douglas

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