II IONIZING RADIATIONS AND CANCER 849 



(Gardner, 1950), inhibits tumor development in an irradiated ovary. It appears 

 that irradiation creates an hormonal imbalance favorable to tumorigenesis in 

 irradiated ovaries (Fig. 36). That testicular hormone does not inhibit irradiation- 

 induced ovarian tumorigenesis has been demonstrated by grafting irradiated ovaries 

 in intact male recipients (Kirschbaum et al., 1956), and by the administration of 

 androgen post-irradiation (Gardner, 1950). 



Partial body X-irradiation (lead-shielded portion of the body containing hemo- 

 poietic tissue) is ineffective in causing leukemia to appear in mice susceptible to the 

 induction of leukemia by irradiation of the endre body (Kaplan, 195 1). The 

 sequence of events demonstrating that the protective agent resides in hemopoietic 

 cells, or is the blood forming ctW per se, follows. Thymectomy prevents the induction 

 of leukemia in C57BL mice by X-rays (Kaplan, 1950a). Radiation of the thymus 

 only or of the whole body except the thymus is not leukemogenic in either case 

 (Kaplan, 1949, 1951). Shielding of a thigh (containing hemopoietic marrow) 

 during X-irradiation also prevents leukemogenesis (Kaplan, 195 1). If the entire 

 animal is irradiated, and bone marrow cells injected post-irradiation, protection 

 is effected (Kaplan et al., 1953); protection against leukemogenesis can be corre- 

 lated with thymic regeneration post-irradiation; in protected mice the thymus 

 regenerates more rapidly (Kaplan^/ al., 1953). Protection against the leukemogenic 

 effects of irradiation parallels protection against lethal effects, the same procedures 

 being efficacious in both instances (Jacobson et al., 1949; Lorenz et al., 195 1). 



Thus, irradiation of target tissue in itself may be non-leukemogenic. Further- 

 more, leukemogenic effects are obtained experimentally from irradiation o^ non-target 

 tissue (Fig. 33, p. 839). Kaplan has demonstrated that grafted thymus undergoes 

 neoplastic transformation if the recipient has been irradiated prior to transplanta- 

 tion of the normal thymus. Not all thymus is sensitive to these "secondary" 

 leukemogenic effects of irradiation ; the genetic constitution of the thymic cells 

 determines their responsiveness. There is some indication that cells of the host 

 which invade the thymic graft may become leukemic only in the thymic environ- 

 ment; otherwise they do not undergo leukemic transformation (Law, 1952). The 

 thymus involutes and then regenerates after grafting; this thymic regrowth may 

 be important in determining susceptibility to neoplastic alteration. 



III. VIRUSES AND CANCER 



{a) Chicken and rabbit tumors 



Although chicken leukemia was the first neoplasm transmitted by a filterable agent 

 (EUerman and Bang, 1908), the passage of the Rous sarcoma (Rous, 191 1) by 

 filtrates was more important to cancer biology. Prior to the discovery of a non- 

 cellular fibrosarcoma agent, which induces fibrosarcomas when inoculated into 

 normal chickens, transmission of neoplasms to new hosts had been accomplished 

 only by inoculation (transplantation) of viable cells into compatible hosts. 



The first suggestion of the viral etiology o{ mammalian neoplasms came from the 

 observations on the Shope papilloma (Shope, 1933). The papilloma of the cottontail 

 can be transmitted to wild rabbits of the same species by skin scarification and 



Literature p. 870 



