title: The inactivation of bacteriophage R17 by ethylating agents: the lethal lesions.
abstract: The biological inactivation of bacteriophage R17 by ethyl methanesulphonate (EMS) and N-ethyl-N-nitrosourea (ENUA) has been studied. At the mean lethal dose for the first compound 8 moles ethyl are bound/mole RNA and with the nitroso compound 3.5 moles ethyl are bound. Analysis of the amounts of the different ethylated derivatives formed shows that the toxicity of the sulphonate can be accounted for by the formation of 3-ethylcytosine, O6-ethylguanine, 1-ethyladenine and chain breaks produced on the hydrolysis of ethyl phosphotriesters. With the nitroso derivative on the other hand, the sum of chain breaks and of bases alkylated on a position involved in specific hydrogen bonding between base pairs only accounts for 65% of the observed toxicity. The possibility that 3-ethyladenine may constitute a lethal lesion is discussed.
mesh_terms: D000478:Alkylation; D001665:Binding Sites; D003090:Coliphages / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000494:pharmacology*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D008698:Mesylates / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D009705:Nucleosides / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism
chemical_list: D008698:Mesylates; D009607:Nitrosourea Compounds; D009705:Nucleosides; D012367:RNA, Viral; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea