Acridine-resistant mutants of T2H bacteriophage.

mechanisms which prevent formation of infective T2H bacteriophage in T ~ c h r i c h i a coli in the presence of acridine dyes are unknown. That interruption of normal maturation occurs in a late stage of phage development was suggested by the work of FOSTER (1948) and has been substantiated physiologically and cytologically. DEMARS, LURIA, FISHER and LEVINTHAL ( 1953) and DEMARS (1955) found in proflavine lysates accumulations of near normal amounts of DNA, serum blocking power, and empty heads (“doughnuts”) ; KELLENBERGER and SECHAUD (1957) found empty heads and tail-like rods but few intact phage in their electron microscopical studies of proflavine lysates. Acridines also may interfere in the actual completion of DNA synthesis. The electrophoretic studies of ASTRACHAN and VOLKIN ( 1957) showed structural differences between T2 DNA extracted from a proflavine lysate and that from a normal lysate. LERMAN (1 961, 1963), by means of sedimentation and viscosity measurements and X-ray diffraction studies, found siipp01-t for the idea that proflavine or quinacrine molecules which were bound to DNA in a phage-dye complex alter the structure of the DNA molecule by intercalation between base pairs. The well-known mutagenic properties of acridincs (DEMARS 1953) have been attributed by ORGEL and BRENNER (1961) to changes in the structure of the DNA molecule, possibly the deletion or addition of bases (BRENNER, BARNETT, CRICK, and ORGEL 1961; CRICK, BARNETT, BRENNER, and WATTS-TOBIN 1961). A study of acridine-resistant mutants of T2, i.e. phage which can grow in proflavine or other acridine dyes, might prove useful in elucidating the sequence of maturation steps or in contributing to understanding of resistance of the infected cells. Four acridine-resistant mutant loci have been mapped genetically and studied to a limited extent physiologically to learn something of their characteristic action. Although the array of places where acridines could act during development complicates the study of resistance to dye action, the present study permits the conclusion that the four mutants represent two unlinked genetic loci which have separate effects on phage maturation. SUSMAN (1963, personal communication), in an earlier study of the action of acridines on T4 bacteriophage development, found two acridine-resistant loci, designated as ac and q (for location on T4 linkage map see PRATT, STENT and HARRIMAN 1961). The T2H mutants resemble those of T4 both in location and behavior.