Nearest Neighbor Affects G:C to A:T Transitions Induced by Alkylating Agents

• Published in: Environmental Health Perspectives [ENVIRON. HEALTH PERSPECT.]. 1987 Vol. 76; pp. 29 - 32
• Main Authors: Glickman, Barry W., Horsfall, Michael J., Alasdair J. E. Gordon, Burns, Philip A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.12.1987
• Subjects: Adducts; Alkylating Agents - pharmacology; Alkylation; Base Composition; Base Sequence; Carcinogens; DNA; DNA Adducts and Repair; DNA Damage; DNA repair; DNA, Bacterial - drug effects; DNA, Bacterial - genetics; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Genes, Bacterial - drug effects; Genetic mutation; Lesions; Molecular Sequence Data; Mutagenesis; Mutation; Nucleotide sequences; Proto-Oncogenes - drug effects; Purines
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.877629

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5′ by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference was not seen following treatment with ethylmethanesulfonate. The observed preference for 5′PuG-3′ site over 5′-PyG-3′ sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells.