Estimation of apurinic/apyrimidinic sites and phosphotriesters in deoxyribonucleic acid treated with electrophilic carcinogens and mutagens. 1980

N R Drinkwater, and E C Miller, and J A Miller

The number of apurinic/apyrimidinic (AP) sites in supercoiled SV40 deoxyribonucleic acid (DNA) after treatment with several electrophilic mutagens was quantitated by electrophoretic analysis of the DNA after cleavage of the phosphodiester bonds adjacent to AP sites by a specific endonuclease. The compounds studied, in order of increasing yields of AP sites obtained on incubation with the DNA for 5 h at 37 degrees C, were dimethylcarbamoyl chloride, ethyl methanesulfonate, N-ethyl-N-nitrosourea, 2-(N-acetoxyacetylamino)fluorene, beta-propiolactone, N-methyl-N-nitrosourea, methyl methanesulfonate, 1'-acetoxyestragole, 4-(N-acetoxyacetylamino)stilbene, (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, N-(benzoyloxy)-N-methyl-4-aminoazobenzene, and 1-pyrenyloxirane. After a 5-h incubation at 37 degrees C and extraction of unreacted compound, further incubation at 70 degrees C generally increased the yield of AP sites; an exception was N-(benzoyloxy)-N-methyl-4-aminoazobenzene-reacted DNA. Except for DNA treated with N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea, which are known to bind to a significant extent to DNA phosphates, the number of alkali-labile lesions in the treated DNA was similar to the number of AP sites. For the compounds studied there was no direct correlation between the number of AP sites produced and missense mutagenic activity, as measured in Salmonella typhimurium strain TA100.

UI MeSH Term Description Entries
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D011119 Polynucleotides BIOPOLYMERS composed of NUCLEOTIDES covalently bonded in a chain. The most common examples are DNA and RNA chains. Polynucleotide
D011685 Purine Nucleotides Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA. Nucleotides, Purine
D011721 Pyrenes A group of condensed ring hydrocarbons.
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004278 DNA, Superhelical Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity. DNA, Supercoiled,DNA, Supertwisted,Supercoiled DNA,Superhelical DNA,Supertwisted DNA
D004587 Electrophoresis, Agar Gel Electrophoresis in which agar or agarose gel is used as the diffusion medium. Electrophoresis, Agarose Gel,Agar Gel Electrophoresis,Agarose Gel Electrophoresis,Gel Electrophoresis, Agar,Gel Electrophoresis, Agarose
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D001080 Apurinic Acid Hydrolysate of DNA in which purine bases have been removed. Acid, Apurinic
D001580 Benzopyrenes A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it. Benzpyrene

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