Erroneous base-pairing induced by a chemical carcinogen during DNA synthesis

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Abstract

THE stability of binding of chemical carcinogens to DNA1–5, in vivo suggests a molecular mechanism for tumour initiation. This interaction may be mutagenic in that it may affect the accuracy with which the modified DNA is copied by cellular DNA polymerases. We now report that the modification of a synthetic polynucleotide template with β-propiolactone increases the incorporation of non-complementary base-paired nucleotides into DNA with the DNA polymerase from either avian myeloblastosis virus (AMV) or sea urchin embryos. Homogeneous AMV DNA polymerase and partially purified sea urchin nuclear DNA polymerase, which are devoid of nuclease activity6,7 were used. β-Propiolactone is a potent mutagen8,9 and carcinogen, initiating tumours in mice10, rats11 and hamsters12. It is an alkylating agent that reacts with guanine and adenine nucleotides in DNA13.

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