Reaction of N-hydroxylamine and N-acetoxy derivatives of 2-amino-3-methylimidazolo[4,5-f]quinoline with DNA. Synthesis and identification of N-(deoxyguanosin-8-yl)-IQ
- 1 June 1988
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 9 (6) , 1061-1065
- https://doi.org/10.1093/carcin/9.6.1061
Abstract
The N -hydroxylamine of the carcinogen 2-amino-3-methylimidazolo[4,5- f ]quinoline (IQ) covalently bound to calf thymus DNA at pH 7, and the binding was 11% higher under acidic conditions (pH 5). The extent of N -hydroxy-IQ binding to single-stranded polynucleotides at neutral pH was in the following order: polyguanylic acid and polyadenylic acid >polycytidylic acid = polyuridylic acid. The binding of the carcinogen to DNA, polyguariyllc acid and polyadenylic acid at neutral pH was enhanced 6-, 4- and 2-fold respectively by the presumed in situ formation of N -acetoxy-IQ from N hydroxy-IQ and acetic anhydride. N -(Deoxyguanosin-8-yl) IQ was synthesized by reaction at pH 7 of N -acetoxy-IQ (formed in situ with N -hydroxy-IQ and acetic anhydnde) with deoxyguanosine and the structure characterized by NMR, mass spectral and UV absorption spectral analyses. Reverse phase HPLC of enzymatically hydrolyzed DNA which had been reacted with N -hydroxy-IQ in vitro showed a major adduct which was chromatographically identical to synthetic N -(deoxyguanosin-8-yl)-IQ. In addition, N -acetoxy-IQ, generated chemically by acetic anhydride or enzymatlcally with mammalian acetyltransferase, formed one major adduct with DNA which was chromatographically identical to the synthetic N -(deoxyguanosin-8-yl)-IQ. The results indicate that N -hydroxy-IQ and N -acetoxy-IQ react with DNA forming primarily the N -(deoxyguanosin-8-yl)-IQ adduct.Keywords
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