188 CELLS, TISSUES, AND ORGANISMS 



range of 50 to 150 roentgens (Puck and Marcus, 1956), or 60 to 200 

 rads, if correction is made for back-scattering e£Fects ( Morkovin and 

 Feldman, 1959). This value for D°, the mean lethal cell dose, is tens to 

 hundreds of times smaller than previous estimates. 



The amount of energy absorption from an ionizing beam that is 

 sufficient to kill a mammalian cell reproductively is equivalent to a 

 temperature rise of less than 0.001° C. This astonishing sensitivity of 

 the mammalian cell has been linked to its chromosomal volume, in 

 which radiation damage has now been demonstrated at doses readily 

 able to account at least for the gross effects so far observed (Puck, 

 Morkovin, and Marcus, 1957). Thus, as little as 25 to 50 roentgens is 

 sufficient to introduce a microscopically visible chromosome break into 

 a normal human cell in vitro, provided that the cells are fixed and 

 stained before the breaks have had time to reseal. When doses suffi- 

 cient to introduce several breaks into the same cell are administered, 

 the complex chromosomal translocations and abnormal recombinations, 

 familiar from cytogenetic studies in simpler organisms, become plenti- 

 ful in mammalian cells irradiated in vitro (Puck, 1958b). Some inves- 

 tigators have reported a lower yield of chromosomal breakage per 

 roentgen, in irradiated euploid human cells of a type differing mor- 

 phologically from those we have described (Bender, 1959). However, 

 it appears to the present author that this apparent divergence may be 

 best explained by the action of factors which prevent the scoring of all 

 of the breaks or aberrations introduced. Such factors, which could 

 cause the number of chromosome breaks scored to appear much smaller 

 than the actual number introduced, have been discussed in detail else- 

 where (Puck, 1958; Wolff, I960); they are strongly dependent on the 

 metabolic conditions, which may vary with the physical and chemical 

 environment, and on the morphological and biochemical state of the 

 cells employed. Dr. E. H. Y. Chu (1959) has confirmed the high chro- 

 mosomal radiosensitivity we reported for normal human cells grown in 

 vitro. 



The demonstration that mammalian cells are extremely sensitive 

 to reproductive death as a result of X-irradiation has gone far in the 

 last few years to explain many of the phenomena of mammalian radio- 

 biology. The survival ciu've for a number of mammalian cell types in 

 vivo, including normal bone marrow ( McCullock and Till, 1960 ) , 

 mouse leukemia cells (Hewitt and Wilson, 1958), and, at least to a 

 first approximation, the fertilized ovum of the mouse (Puck, 1960b; 

 Russell and Russell, 1954 ) , have been shown to correspond very closely 

 to the single-cell survival curve of the mammalian cell in vitro (Puck 

 and Engelberg, 1960). Thus the contribution of cellular reproductive 

 damage to the total complex of the pathology constituting mammalian 

 radiation syndrome appears to bear out the earlier predictions of its 



