The removal of alkylation products from the DNA of Escherichia coli cells treated with the carcinogens N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea: influence of growth conditions and DNA repair defects. 1980

W Warren, and P D Lawley
Institute of Cancer Research: Royal Cancer Hospital, Pollards Wood Research Station, Nightingales Lane, Chalfont St. Giles, Bucks HP8 4SP, UK.

Cultures of Escherichia coli were treated with alkylnitrosoureas. The rates of removal of methylation and ethylation products from the DNA of strains defective in various repair pathways were compared with those of their respective wild-type strains. It was found that the removal of O6-methylguanine did not depend upon xth gene function or the uvr endonuclease. However, the rate of elimination of this product was markedly decreased in polA strains. O6-Ethylguanine (in contrast to its methyl analogue) was removed more slowly from the DNA of uvrA(-) than from that of uvrA(+) strains, indicating that the removal of O6-ethylguanine can be initiated by the uvr endonuclease. The composition of the medium in which methylated cells were resuspended following treatment with N-methyl-N-nitrosourea was also found to influence the rate at which O6-methylguanine was removed from the DNA of treated bacteria. No significant removal of this product from bacterial DNA occurred during treatment of cells in buffer, or when treated bacteria were resuspended in salts medium or in growth medium containing chloramphenicol. The results indicate that the elimination of O6-methylguanine, but not of 3-methyladenine, requires protein synthesis. Only very limited constitutive activity capable of removing O6-MeGua was detected.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D008770 Methylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosomethylurea,N-Methyl-N-nitrosourea,NSC-23909,N Methyl N nitrosourea,NSC 23909,NSC23909
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
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005038 Ethylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosoethylurea,N-Ethyl-N-nitrosourea,N Ethyl N nitrosourea
D006147 Guanine
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin
D000477 Alkylating Agents Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. Alkylating Agent,Alkylator,Alkylators,Agent, Alkylating,Agents, Alkylating

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