3. Shapes of Survival Curves for Acutely Responding and Late Responding Normal

It is now possible to construct dose survival curves for many normal tissues in vivo. However, for those tissues for which clonogenic assays do not exist because the target cells in the tissue are either unknown or cannot be quantitatively assessed, survival curves can only be deduccd from their dose response curves. Based on such deductions, it has been suggested that not only do acutely and late responding normal tissues express their damage at vastly different times, but that their survival curves for the "target" cells are also different. Shown in Figure 7-10 are dose survival curves for an acutely responding and a late responding normal tissue. It is clear that the shapes of the survival curves for the two classes of tissue differ, and that the curve for late responding normal tissues is "curvier" than that for acutely responding normal tissues. Some knowledge of the differences in survival curve shapes is important to an understanding of the factors that govern cellular and tissue responses, since modifiers of radiation damage may differentially affect these two classcs of normal tissues. This hypothesis has important implications for dose fractionation as used in radiotherapy.

TABLE 7-5

Quantitative Normal Tissue IZndpoints

Tissue	Clonogenic	Functional	Lethality
Bone marrow	Spleen colonies (transplantation)		LDj(|/3i) davs
Intestine	Crypt colonies (in situ)		LD50/7. 10 dn\s
Testis	Tubules with spermalogonic epithelium (in situ)	Weight
Skin	Skin colonies (in situ)	Early skin reaction, late defonnites
Esophagus	-	-	LD 50/28- 6(1 days
Mammary	Tpansplantation	-
gland
Liver	In situ	-	-

/ О

Thyroid	Tpansplantation	-	-
Kidney	Tubules with epithelial cclls	"Cr EDTA clearance, hematocrit, urination frequency, weight	LD50/12- 15 mos
Lung	-	Breathing rate, C02	LD50/8O- I80days
		clearance	LD5O/36O Oil VS
Bladder		Urination frequency, contracture
CNS			Incidence of paralysis, LD50/7 mos. LD50/1X mos.

ПС 7-10.

Schematic of the hypothesized survival с urnes for acutely responding and late responding normal tissues. The curve for the late responding normal tissues is "curvier" than that for the acutely responding normal tissues.