Inactivation of bacteriophage lambda and lambda DNA by nitrogen mustard.
Bacteriophage lambda and lambda DNA were treated with alkylating agents. The survival of phage was assayed by infectivity and that of DNA by infectivity of phage particles assembled from the DNA in vitro. Phage lambda were more sensitive to nitrogen mustard (C1(CH2)2NMe(CH2)2C1; HN2) than was lambda DNA. The inactivation of lambda DNA was biphasic; the second component of the inactivation was sensitive to mutations allelic for recA, polA and uvrB. This behaviour was not shown by pBR322 plasmid DNA treated with HN2 nor by lambda DNA treated with monofunctional alkylating agents (or HN2 if the second alkylation reaction was stopped by addition of a mercaptan). From Arrhenius plots, the activation energy for the reactions with DNA and interact phage were found to be different. The activation energy for the inactivation of intact phage was the same as that (measured independently) for the predominant reaction (or class of reactions) in which HN2 cross-links DNA to protein in lambda particles. From these data we conclude that the inactivation of lambda by HN2 is due, primarily, to DNA-protein cross-linking. The implications for the mode of action of DNA-reactive bifunctional anti-viral and cytotoxic compounds are discussed.
D000998:Antiviral Agents; D010582:Bacteriophage lambda / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D008466:Mechlorethamine / Q000494:pharmacology*
D000998:Antiviral Agents; D004279:DNA, Viral; D008466:Mechlorethamine