328 F. JACOB AND E. L. WOLLMAN 



1. Genetic Factor 



Exposure to UV light may induce phage development only in some lyso- 

 genic systems. Within the same bacterial species, both inducible and non- 

 inducible strains can be isolated (lonesco, 1951; Jacob, 1952c). Since a 

 lysogenic system may be visuaUzed in terms of an association between the 

 bacterial host and the prophage, the question arises of whether one or the 

 other component or the whole system is responsible for the character of 

 inducibility. The answer to this question can be obtained by isolating lyso- 

 genic clones after infection of various sensitive strains of bacteria with various 

 strains of temperate phages. In most of the systems which have been investi- 

 gated so far, inducibihty behaves as a characteristic of the prophage, although 

 an exception to this rule has recently been reported (lonesco, 1956). In fact, 

 as will be seen later, the inducible character of a prophage seems to depend 

 upon its location on the genetic apparatus of the host. In most of the lyso- 

 genic systems, inducibility and rate of spontaneous production appear to be 

 correlated, the spontaneous production of inducible strains being higher 

 than that of noninducible strains. 



2. Inducing Agents 



Inducing properties have been recognized for a number of agents. Physical 

 agents, such as UV hght (Lwoff et al., 1950), X-rays (Latarjet, 1951), as well 

 as y-rays (Marcovich, 1956a), are very efficient. Among the chemicals that 

 have been shown to act as inducers are nitrogen mustard (Jacob, 1952d; 

 Williams-Smith, 1953), organic peroxides, epoxides, and ethyleneimines 

 (Lwoff and Jacob, 1952), and azaserine (Gots et al., 1955). Hydrogen peroxide 

 also induces phage formation m certain inducible strains, either when 

 directly added (Lwoff and Jacob, 1952), or when produced in a nascent state 

 by addition of sulfhydril compounds in the presence of copper (Lwoff and 

 Siminovitch, 1952). Leucovorin previously irradiated with UV light has also 

 been reported to have some inducing action (Borek and Rockenbach, 1955). 



Most of these inducing agents also exert, in other systems, either muta- 

 genic or carcinogenic activities. However, certain chemicals whose activities 

 as mutagens or carcinogens have been demonstrated, do not induce phage 

 production in those systems in which they have been assayed. This is the 

 case with ethyl-urethane, caffeine, and also several water-insoluble carcino- 

 gens, such as methylcholanthrene and dibenzanthracene, the latter probably 

 because they cannot penetrate inside bacteria. For those mutagens or car- 

 cinogens which may act as inducing agents, lysogenic bacteria provide a very 

 sensitive test, since the probability of inducing phage development is in most 

 cases very close to one. 



