Abstract
An important step in carcinogenesis is thought to be the initial attack of the DNA molecule by a so-called ultimate carcinogen. More than 90% of the carcinogens tested have been found to be mutagens in bacterial systems1. The covalent binding of the ultimate carcinogen to the DNA bases or phosphate groups creates a premutational lesion that in vivo is processed by the repair, replication and recombination enzymes, and eventually may be converted into a mutation. Being interested in the way that an initial premutational event is converted into a stable heritable mutation, we have sequenced stable mutations in a gene that has formed covalent adducts in vitro with N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF, a model for the ultimate metabolite of the rat liver carcinogen 2-acetylaminofluorene AAF). We show here that the mutations are mainly frameshifts involving G · C base pairs, and that certain base pairs (hotspots) are affected at relatively high frequences. These results fit a model in which N-AcO-AAF-modified guanine acts as a non-coding base that during replication results in deletion of the modified residue.
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Fuchs, R., Schwartz, N. & Daune, M. Hot spots of frameshift mutations induced by the ultimate carcinogen N- acetoxy-N-2-acetylaminofluorene. Nature 294, 657–659 (1981). https://doi.org/10.1038/294657a0
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DOI: https://doi.org/10.1038/294657a0
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