In vitro replication studies of oligonucleotides containing site-specific DNA adducts in frameshift-prone sequences

Abstract

Exposure to endogenous and exogenous chemicals can lead to modification of DNA and potentially lead to cancer. Frameshift mutations may be a consequence of these modifications to DNA. Oligonucleotides were synthesized that contain a site specific a site specific C8-deoxyguanosine adduct 2-amino-3-methylnaphtho[1,2-d]imidazole (CCIQ), which is an analogue of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and the adducts R- and S-á-methyl-ã-hydroxy-1,N2-propano-2’-deoxyguaosine and ã-hydroxy-1,N2-propano-2’-deoxyguanosine in frameshift prone sequences. In vitro replication studies were conducted to examine which nucleotide was incorporated opposite the adducts by a variety of DNA polymerases. The sequence and yields of the extension products were determined using tandem mass spectrometry.