THE PROBABLE CHEMICAL NATURE OF CROWN‐GALL TUMOR‐INDUCING PRINCIPLE

Abstract

IT HAS BEEN DEMONSTRATED that specific etiological agent-ttumor-inducing principle-is required as one of several agents and factors which, acting in sequence, transform normal cells into crown-gall tumor cells (Braun, 1947b). The temporal relation of tumor-inducing principle (TIP) to the transformation processes was investigated by Braun (1947a, 1952) and Braun and Mandle (1948), who showed that it was active subsequent to conditioning period and just prior to or during the first histologically detectable stages of wound healing. Thus, TIP begins acting on conditioned cells about 24 hr. after inoculation of crown-gall bacteria into healthy tissues. The period of its activity can be as short as 10 hr. under optimal conditions. Braun and Mandle (1948), in an extension of earlier studies (Riker, 1926), found that the principle apparently is destroyed or inactivated in vivo at 320C. at about the same rate as it is formed at 25?C. At 28?C. to 31?C. the rate of formation to TIP exceeded its rate of destruction. Braun (1950) reported that the activation energy for TIP inactivation was about 80,000 cal./mole and suggested that TIP or something intimately associated with its inactivation, may be . . . a factor of complex structure. Although conclusive data are lacking, it may be assumed that TIP is product of virulent crowngall bacteria synthesized by the bacteria in the host. The suppression of tumor cell formation by antibiotics (de Ropp, 1949) or by bacteriophage treatments of crown-gall bacteria (Brown and Quirk, 1929) supports this assumption. Klein and Klein (1953) showed that completely avirulent strains of crown-gall bacteria, as well as avirulent species of related bacteria, could acquire the property of virulence from nucleic acids produced by virulent forms and from the DNA isolated from virulent bacteria. This transmittance factor had no tumor-inducing ability and is not TIP. Once acquired, virulence appeared to be genetically fixed, indicating that hereditary units for virulence were acquired by bacteria deficient for these units (Cf. Lederberg, 1952). The formation of TIP by virulent bacteria thus seems to be conditioned by the presence and activity of hereditary units which regulate the production of the principle. Attenuated cultures of crowngall bacteria, on the other hand, appear to possess the ability to form TIP but apparently lack the abil-