Induction of mutations in the lac region of Escherichia coli strain S1.

is a group of chemicals, including nitrogen mustards, acridines, nitroT::gnidine, azaserine, nitrofurazone, mitomycin, nitrous acid, and 2-aminopurine, which, despite their diverse chemical or physical properties (see review by FREESE, 1963), share many biological properties among themselves and with ultraviolet radiation (UV) in affecting microorganisms. They are mutagenic; several of them induce temperate phage in the prophage state; in certain sensitive strains of bacteria (e.g., Escherichia coli B) they inhibit cell division mechanisms causing filaments to be formed; some specifically inhibit DNA synthesis and cross-link DNA. Most significant, however, is the observation that mutants of a sensitive strain such as E. coli S or B selected for resistance to any one of these agents are almost invariably found to be resistant to all the other agents and to UV ( WOODY-KARRER and GREENBERG 1964; ZAMPIERI and GREENBERG 1964, 1965a). Furthermore, the amount of lethal damage induced by most of these chemicals and by UV in a sensitive strain is dependent on post-treatment conditions such as the composition of the plating medium and the temperature of incubation (ZAMPIERI and GREENBERG 196513). These facts argue that all these chemicals have a common effect on a common target, presumably DNA, which is repaired in resistant strains by a common mechanism. The last idea is reinforced by the observation that resistance to these agents as well as to UV can be transferred as a single gene by conjugation from resistant donor strains of E. coli to recipient sensitive strains (GREENBERG 1964). The idea is further reinforced by the observations that the so-called dark reactivation process in bacteria (HCR) which is also under the control of each of several, presumably independent, genes ( HOWARD-FLANDERS, BOYCE, SIMSON and THERIOT 1962; HOWARD-FLANDERS, BOYCE and THERIOT 1966) is able to excise not only thymine dimers induced in DNA by UV (BOYCE and HOWARD-FLANDERS 1964; ETLOW and CARRIER 1964) but also alkylated purines produced by mustards (LAWLEY and BROOKES 1965; PAPIRMEISTER and DAVISON 1964). One might expect that if, in a sensitive strain of bacteria such as E. coli strain S , all the radiomimetic agents as well as UV have a common effect, that this might be reflected in mutually revertible mutations induced by these agents. This report will show that mutations to Lac(inability to ferment lactose) induced in strain S by any of the chemicals and UV were revertible by all the other chemicals and UV. ' 1 his wroih was carried nut under Public IIealth Senice Grant CA 05OR7-00 Piesent address Institute of M m d m l o g l , Faculty of &ledlane. Milan, Italq Ret pient of d Public IIedth Seivice Lareer Dexelopment hwaid