The induction of errors during in vitro DNA synthesis following chloroacetaldehyde-treatment of poly(dA-dT) and poly(dC-dG) templates.
AffiliationPaterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX
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AbstractChloroacetaldehyde, a rearranged metabolic product of the human carcinogen vinyl chloride, reacts with the DNA-like polymers poly(dA-dT) and poly(dC-dG) to form etheno-adducts of the adenine and cytosine bases. These treated polymers, when used as templates for E. coli DNA polymerase I in an in vitro assay, show a decreased ability to direct DNA synthesis. At the same time, increased relative levels of non-complementary nucleotides are incorporated. With the poly(dA-dT) templates 1 dGMP residue is incorporated for every approx 60 ethenoadenine residues present whilst no increased misincorporation of dCMP was detected. With the poly(dC-dG) templates 1 misincorporation of dAMP or dTMP occurred in the presence of approx 30 and 80 ethenocytosine residues respectively. A nearest neighbour analysis shows that with the modified poly(dC-dG) templates the majority of the errors were incorporated opposite cytosine (or modified cytosine) bases.
CitationThe induction of errors during in vitro DNA synthesis following chloroacetaldehyde-treatment of poly(dA-dT) and poly(dC-dG) templates. 1981, 2 (2):141-6 Carcinogenesis