1190 RADIATION BIOLOGY 



Mutagens are numerous, and ionizing radiation acting directly on a 

 "sensitive" part of the cell is one of them. Others may be endogenous 

 in origin. 



Experiments were reported showing that cholesterol exposed to massive 

 doses of X radiation (about 60,000 r) acquires carcinogenic power (Bur- 

 rows and Mayneord, 1937), but this finding has not been confirmed. 

 This and other ideas such as the transformation of an endogenous steroid 

 into a carcinogenic hydrocarbon and the meaning of the presence of 

 carcinogens in tissue extracts, are fully discussed by Lacassagne in his 

 monograph on cancers produced by endogenous substances (1950). 

 Concerning problems common with carcinogenesis by ultraviolet rays, 

 see Rusch (1949) and Blum (1953). 



The assumption of indirect carcinogenesis by endogenous carcinogens 

 is also speculative, as no one has yet proved that endogenous carcinogens 

 isolated from the body exist in that form and are not the products of the 

 chemical techniques used for their isolation. Suggestive evidence for 

 the mutation theory is furnished by studies on the genetic character of 

 the neoplastic cells (Furth et al., 1944), by demonstration of mutagenic 

 power of some carcinogens (Demerec, 1948, and Latarjet et al., 1949), the 

 carcinogenic power of some mutagens (Boyland and Horning, 1949; 

 Burdette, 1950; and Heston, 1950), and by the character of mitotic 

 abnormalities, but direct demonstration of a chromosonal change is 

 lacking. Mottram (1931) tested the validity of the somatic mutation 

 hypothesis by exposing cells in vitro to high concentration of carbon 

 dioxide and rays which, in Drosophila, gives rise to derangements of 

 chromosomes. The irradiated cells were reimplanted in the animal 

 but only one testicular tumor was produced. Such experiments are 

 cumbersome, yet are worth pursuing to find out whether the thesis, that 

 mutation is proportional to the dose, applies to carcinogenesis. 



That tissues which are subjected to an increased physiological or patho- 

 logical regenerative process are more susceptible to neoplasia induction 

 than normal tissues has long been demonstrated by several investigators. 

 This may, in part, be due to the presence of an increased number of cells 

 in a sensitive (mitotic) phase. The mere fact that ionizing radiation is 

 one of the most powerful agents causing genetic alterations (Muller, 

 1938; Catcheside, 1948) lends strong support to the somatic mutation 

 theory of cancer. 



Based on studies of Polytoma uvella, Lacassagne (1936) postulates five 

 types of lesions in the cell: (1) temporary suppression of growth due to 

 absorption of energy in the cytoplasm (associated with a reparable injury 

 to mitochondria and other cytoplasmic structures), (2) destruction of 

 parts of chromatin resulting in abortive anomalies of division, (3) sup- 

 pression of reproduction due to injury of centrosomes, (4) suppression of 

 motility due to injury of motor centers, and (5) immediate death of cell. 



