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Effect of DNA sequence, ionic strength, and cationic DNA affinity binders on the methylation of DNA by N-methyl-N-nitrosourea

Journal Article · · Chem. Res. Toxicol.; (United States)
DOI:https://doi.org/10.1021/tx00003a003· OSTI ID:6615375

DNA alkylation by N-alkyl-N-nitrosoureas is generally accepted to be responsible for their mutagenic, carcinogenic, and antineoplastic activities. The exact nature of the ultimate alkylating intermediate is still controversial, with a variety of species having been nominated. The sequence specificity for DNA alkylation by simple N-alkyl-N-nitrosoureas has not been reported, although such information is basic in understanding the specific point mutations induced by these compounds in oncogene targets. These two points are addressed by using N-methyl-N-nitrosourea methylation of a 576 base-pair /sup 32/P-end-labeled DNA restriction fragment and high-resolution polyacrylamide sequencing gels. This method provides information on the formation of N/sup 7/-methylguanine, by the generation of single-strand breaks upon exposure to piperidine.

Research Organization:
Univ. of Nebraska Medical Center, Omaha (USA)
OSTI ID:
6615375
Journal Information:
Chem. Res. Toxicol.; (United States), Journal Name: Chem. Res. Toxicol.; (United States) Vol. 1:3; ISSN CRTOE
Country of Publication:
United States
Language:
English