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Mutagenic Potency of Exocyclic DNA Adducts: Marked Differences Between Escherichia coli and Simian Kidney Cells
M. Moriya, W. Zhang, F. Johnson and A. P. Grollman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 91, No. 25 (Dec. 6, 1994), pp. 11899-11903
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2366244
Page Count: 5
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A single-stranded shuttle vector containing a single 3,N4-etheno-2'-deoxycytidine (ε dC) or 1,N2-(1,3-propano)-2'-deoxyguanosine (PdG) DNA adduct was used to investigate translesional DNA synthesis in Escherichia coli and simian kidney (COS) cells. The presence of either exocyclic adduct was associated with reduced numbers of transformants. In E. coli, this inhibitory effect could be overcome partially by irradiating cells with UV light before transformation. Translesional synthesis past both exocyclic lesions was accompanied by targeted mutations. For PdG, the primary mutagenic events observed in both hosts were PdG $\longrightarrow$ T transversions; in preirradiated E. coli, PdG $\longrightarrow$ A transitions were also observed. The targeted mutation frequency for single-stranded DNA that contained PdG was 100% in nonirradiated E. coli, 68% in preirradiated cells, and 8% in COS cells. In contrast, the targeted mutation frequency for single-stranded DNA that contained ε dC was 2% in nonirradiated E. coli, 32% in preirradiated cells, and 81% in COS cells. The primary mutations generated by εdC in both E. coli and COS cells were εdC $\longrightarrow$ A and εdC $\longrightarrow$ T base substitutions. These observations appear to reflect the variable specificity of DNA replication complexes in incorporating bases opposite certain adducts. We conclude that DNA synthesis past the same DNA adduct can have strikingly different consequences in bacteria and mammalian cells, underscoring the importance of establishing the intrinsic mutagenic potential of DNA adducts in mammalian cells.
Proceedings of the National Academy of Sciences of the United States of America © 1994 National Academy of Sciences