Environmental mutagens that induce the adaptive response to alkylating agents in Escherichia coli.
Many microorganisms exhibit an adaptive response to mutagenic alkylation damage. In Escherichia coli the response is regulated by the inducible Ada protein. A sensitive immunoassay employing two anti-Ada monoclonal antibodies has been developed here to monitor low levels of induction of the Ada protein. This protein was detected in non-induced E. coli which contained an average of two molecules of Ada per cell. The occurrence of the adaptive response in bacteria signals the existence of an ecological niche in which cells are exposed to direct-acting methylating compounds, but the structure and identity of these agents are unknown. Using the immunoassay to search for possible candidates, a number of methylating agents and precursors of such agents have been investigated. Carbamyl phosphate and methylamine yield N-methylurea, which reacts subsequently with nitrite to generate the strong inducer N-methyl-N-nitrosourea. The antibiotic streptozotocin also is a potent inducer of the adaptive response. Moreover, the abundant environmental mutagen methyl chloride acts as an inducer.
Vaughan
P
P
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
Sedgwick
B
B
Hall
J
J
Gannon
J
J
Lindahl
T
T
D000222:Adaptation, Physiological / Q000187:drug effects; D000477:Alkylating Agents / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D004260:DNA Repair; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D029968:Escherichia coli Proteins; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007424:Intracellular Fluid / Q000378:metabolism; D008737:Methyl Chloride / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D008780:Methyltransferases / Q000378:metabolism; D008782:Methylurea Compounds / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014157:Transcription Factors
D000477:Alkylating Agents; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D002274:Carcinogens, Environmental; D029968:Escherichia coli Proteins; D008782:Methylurea Compounds; D009153:Mutagens; D014157:Transcription Factors; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D008737:Methyl Chloride; D003404:Creatinine; D008780:Methyltransferases; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase; C067511:Ogt protein, E coli; C002352:methylurea