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Effects of vitamin A on the metabolism and mutagenicity of 2AAF in vitro and on the covalent binding to rat liver DNA/RNA in vivo

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Abstract

Vitamin A has been shown to affect the in vitro metabolism of 2AAF. At low concentrations of retinol or retinyl palmitate, a decreased production of ring-hydroxylated as well as deacetylated and TV-hydroxylated metabolites was observed, measured by high performance liquid chromatography. The increased mutagenicity of 2AAF observed after addition of vitamin A in the Ames test cannot therefore be explained as a result of stimulated N-hydroxylation. However, the addition of retinol was found to enhance the mutagenicity of the metabolite N-OH-2AAF in the presence of an S-9 fraction of rat liver homogenate. No differences with regard to the covalent binding of 2AAF or its metabolites to rat liver DNA/RNA in vivo could be demonstrated in animals fed diets with normal or high vitamin A content.

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Abbreviations

2AF:

2-aminofluorene

2AAF:

2-acetylaminofluorene

GLU-P-1:

2-amino-6-methyl-dipyrido(1,2-a∶3′,2′-d)imidazol

GLU-P-2:

2-amino-dipyrido(1,2-a∶3′,2′-d)imidazol

N-OH-2AAF:

N-hydroxy-2-acetylaminofluorene

OAAT:

orthoaminoazotoluene

TRP-P-1:

3-amino-3,4-dimethyl-5H-pyrido(4,3-b)indole

TRP-P-2:

3-amino-1-methyl-5H-pyrido(4,3-b) indole

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Rondahl, L., Busk, L., Ahlborg, U.G. et al. Effects of vitamin A on the metabolism and mutagenicity of 2AAF in vitro and on the covalent binding to rat liver DNA/RNA in vivo. Arch Toxicol 57, 178–183 (1985). https://doi.org/10.1007/BF00290884

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