Mutagenicity of the 1-Nitropyrene-DNA Adduct N- (Deoxyguanosin-8-yl)-1-aminopyrene in Mammalian Cells
2007
The mutagenesis of the major DNA adduct N-(deoxyguanosin-8-yl)-1-aminopyrene (C8-AP-dG) formed by 1-nitropyrene was compared with the analogous C8-dG adducts of 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF) in simian kidney (COS-7) cells. The DNA sequence chosen for this comparison contained 5′-CCATCGCTACC-3′ that has been used for solution NMR investigations. The structural and conformational differences among these lesions are well-established [Patel, D. J.Mao, B.Gu, Z.Hingerty, B. E.Gorin, A.Basu, A. K.Broyde,S. (1998) NMR solutionstructures of covalent aromatic amine-DNA adducts and their mutagenicrelevance. Chem. Res. Toxicol. 11, 391–407.]. Accordingly, we found a notable difference in the viability of the progeny, which showed that the AAF adduct was most toxic and that the AF adduct was least toxic, with the AP adduct exhibiting intermediate toxicity. However, analysis of the progeny showed that translesion synthesis was predominantly error-free. Only low-level mutations (<3%) were detec...
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