628 RADIATION BIOLOGY 



on sectioned material, in which induced breaks were not easily diagnosed. 

 Moreover, adequate consideration was not given to the effect on the 

 induced reaction of the length of time elapsing between irradiation and 

 fixation of the cell. 



Recognizing the need for a more extensive evaluation of these factors, 

 Alberti and Politzer (1923, 1924) examined entire cells of the corneal 

 epithelium of salamander larvae, fixed at varying periods of time after 

 the animals had been exposed to X-ray treatments of different intensities. 

 The observed types of cellular disturbance were interpreted as revealing 

 a reaction system that involves (1) a period of "primary effect," begin- 

 ning shortly after irradiation, characterized by a decline in the frequency 

 of mitoses and the appearance, especially after treatment with high doses, 

 of pycnotic nuclei with adherent chromosomes, (2) a subsequent period 

 of mitotic inactivity, and (3) a period of "secondary effects," character- 

 ized by abnormal mitoses with fragmented or reconstituted chromosomes, 

 whose frequency is dependent on the duration of the treatment. 



It is now recognized that during the period of "primary" or "physio- 

 logical" effect the materials of the chromosomes are altered, and the 

 mitotic mechanism governing the normal orderly distribution of the 

 chromatids into daughter nuclei is inhibited. In cells that have been 

 exposed to moderate doses of radiation, the chromosomes in late prophase, 

 metaphase, or anaphase stages may continue the course of division, but 

 the mitotic progress of cells in earlier prophases is arrested, and at times 

 their chromosomes evince regressive changes that suggest a return to 

 interphasic conditions (see, for example, Carlson, 1940). Because the 

 onset of new mitoses is inhibited, there occurs shortly after irradiation 

 a period of mitotic inactivity, in which practically all cells appear to be 

 in resting stages. If the treatment has not been too intense, the mitotic 

 rhythm may subsequently be reestablished, whereupon the condensed 

 chromosomes may reveal various types of induced abnormalities. At 

 times the delay effected by radiation may be followed by precocious 

 differentiation of the treated cells (e.g., primary spermatocytes into giant 

 spermatids, Creighton and Evans, 1941). 



When the treatment is more drastic, the chromonematic threads of 

 early mitotic stages may reveal nodal thickening along their lengths, and 

 the condensed chromosomes may adhere or clump to form irregular 

 aggregates of chromatin material, presumably as a consequence of changes 

 in viscosity of component proteins and nucleic acids. Such alteration 

 disrupts the normal pattern of chromosome division, at times producing 

 bizarre mitotic figures (see, for example, Helwig, 1933, White, 1937, 

 Carlson, 1938a, Carothers, 1940, Creighton and Evans, 1941, and Bishop, 

 1942, on grasshopper cells; Bauer and LeCalvez, 1944, on eggs of Ascaris; 

 Tansley, Gray, and Spear, 1948, Duryee, 1949, and Rugh, 1950, on 

 amphibian cells; Welander et al., 1948, on cells of embryos and larvae of 



