200 G. W. CASARETT 



short-lived, age and die, but are replaced by the activity of vegetative and 

 differentiating inter-mitotic precursor cells. 



In tissues containing the radiation sensitive vegetative and differentiating 

 inter-mitotic parenchpnal cells, such as epidermis, gastro-intestinal mucosae, 

 and haematopoietic tissues, the early radiation destruction of these cells 

 depends relatively little on the early radiation damage of vasculo-connective 

 tissue, but the degree of damage to fine vasculature and the change in 

 connective tissue seems to be generally greater in such tissues than in tissues 

 with radiation-resistant parenchymal cells receiving similar doses. Following 

 total-body doses in the sublethal life-shortening range, the radiation sensitive 

 parenchyma is regenerated after destructive effects to normal or subnormal 

 levels of cellularity while vasculo-connective tissue-changes are irreversibly 

 "fixed" and progress with passing time to an advanced level as compared with 

 non-irradiated tissue (Fig. 4; Hursh et al, 1958). Eventually there is another 

 phase (phase IV) of gradual loss of parenchymal cells secondary to these 

 progressive changes in supporting tissues and premature as compared with 

 non-irradiated tissues. The intermediate period (phase III) of maintained 

 parenchymal cellularity between the period of regeneration and the beginning 

 of the period of the age involution is shorter the larger the dose, owing to the 

 fact that the vasculo-connective-tissue changes are greater the larger, or more 

 intense, the dose. This intermediate period corresponds to the period of 

 relatively low mortality rate between the period of acute, or subacute, 

 mortality and the late period of age-dependent mortality. 



With the larger doses that can be administered to such tissues under 

 conditions of localized irradiation, there is greater damage to vasculo- 

 connective tissue and greater destruction of parenchyma, that is, directly and 

 sometimes also secondary to marked vascular damage. There is also reduced 

 and delayed regenerative activity of remaining parenchymal cells, due to 

 damage of fine vasculature and connective tissue, and a shorter intermediate 

 period between the regenerative phase and the later involutional phase. In 

 fact, with sufficiently high doses, there is no intermediate period due to failure 

 of regeneration and the development of early fibro-atrophy of the tissue. 



In the case of tissues containing the radiation-resistant reverting post- 

 mitotic parenchymal cells, such as hver and kidney and many other epithelial 

 glands, and tissues containmg the irreplaceable, radiation-resistant, fixed 

 post-mitotic parenchymal cells, such as muscle and brain and spinal cord, 

 early radiation destruction of considerable numbers of parenchymal cells in 

 direct, or indirect, fashion requires relatively large doses. Consequently, 

 early destruction of considerable numbers of these parenchymal cells is not 

 seen with total -body irradiation in the sublethal dose range, but only with 

 more intensive localized, or generalized, irradiation. However, with sublethal 

 irradiation of the whole-body the vasculo-connective tissue changes may be 



