The response of pig skin to single and fractionated high dose-rate and continuous low dose-rate 137Cs-irradiation-III. Re-evaluation of the CRE system and the TDF system according to the present findings

Application of the cumulative radiation effect (CRE) and time dose fractionation factors (TDF) systems on the dose-effect data from single and fractionated irradiation at high dose rate and continuous irradiation at low dose rate on pig skin revealed that significant corrections of these empirical models are necessary. There is evidence for modification of the CRE and TDF-formula for fractionated high dose-rate irradiation concerning late effects on normal tissue. The pig skin result indicated a value of the normalizing constant of 0.57 and 2.02 in the CRE and TDF-formulae for continuous irradiation instead of the proposed value of 0.80 and 1.57 respectively. The practical consequences for prediction of equivalent normal tissue reactions for fractionated high dose-rate and continuous low-dose-rate irradiation by the CRE and TDF systems will be elucidated.     

The response of pig skin to single and fractionated high dose-rate and continuous low dose-rate 137Cs-irradiation--II. Theoretical considerations of the results.

The result of a comparison of single and fractionated irradiation at high dose rate with continuous irradiation at low dose rate on pig skin is discussed from a radiobiological point of view. A short review is given of other fractionation and dose-rate investigations. Some dose-rate experiments have resulted in an increased therapeutic gain for continuous irradiation at low dose rate, compared to single acute irradiation. However, there is a lack of data comparing fractionated high dose-rate irradiation with continuous low dose-rate irradiation on normal tissues as well as malignant tumors.     

Functional and morphological changes in pig skin after single or fractionated doses of X rays

The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days ($\text{6}\text{f}\text{18}$ days; 3780 cGy) or 30 fractions in 39 days ($\text{30}\text{f}\text{39}$ days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the $\text{30}\text{f}\text{39}$ days treatment group. The second wave (10–16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the $\text{30}\text{f}\text{39}$ days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after $\text{6}\text{f}\text{18}$ days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation ($\text{30}\text{f}\text{39}$ days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the $\text{30}\text{f}\text{39}$ days group than in the other treatment groups. Isotope clearance was similar to that in normal skin, as was the vascular density of the dermis. The return of these parameters to normal was correlated with the development of dermal atrophy.     

The in vivo radiation response of an experimental tumor: the effect of exposing tumor-bearing mice to a reduced oxygen environment prior to but not during irradiation.

The effect of single or fractionated doses of radiaton on the transplantable KHT sarcoma has been studied in mice which were exposed to a reduced oxygen (O₂) environment prior to but not during irradiation. Tumor-bearing mice were kept in a 12% O₂ environment for a period of time; then their tumors were irradiated locally with a single dose of 2000 rad at a dose rate of 1140 rad/min while the mice breathed air, O₂ or carbogen (5% CO₂:95% O₂). Following irradiation, tumor cell survival was determined using an in vivo lung colony or an in vitro agar colony assay.The results indicate that overnight exposure of tumor-bearing mice (15 hr) to 12% O₂, prior to irradiation of their tumors under air-breathing conditions, leads to a reduction in tumor cell survival by a factor of 3–4 over that found for tumors of air-breathing mice not given a low O₂ pre-treatment. A similar reduction in tumor cell survival is observed for irradiation without prior exposure to the low O₂ environment when the mice are given O₂ or carbogen to breathe instead of air. If the tumors are irradiated while the animals breathe O₂ or carbogen after exposure to 12% O₂, tumor cell survival is reduced to a value ～10 times lower than is obtained in tumors of air-breathing mice not given a low O₂ pre-treatment.During a course of fractionated radiation (seven 500 rad fractions at 24 hr intervals) delivered while the tumor-bearing mice breathed air or carbogen, a 12% O₂ exposure prior to alternate dose fractions was found to lead to significant enhancement of tumor cell killing above that observed when no pre-treatment with 12% O₂ was employed. The reduction in tumor cell survival almost certainly results from a decrease in the number of hypoxic cells in the tumors but the mechanism by which this reduction occurs is not known at present. The decrease may be because of direct killing of hypoxic cells by the low O₂ environment or because of physiological adaptation to the low O₂ environment which persists when the animals are returned to an air atmosphere, leading to an improved O₂ delivery to the tumor. A number of adaptation mechanisms were studied but these shpwed little correlation with the radiobiological effect. Consequently, no clear explanation of the results can be given at present. Regardless of the mechanism, the findings indicate an approach to increasing the effectiveness of radiation treatment of tumors.     

^125I粒子持续低剂量率照射对前列腺癌PC-3细胞移植瘤的抑制作用

目的：探讨^125I粒子持续低剂量率照射对前列腺癌PC-3移植瘤体内抑制作用的疗效,为前列癌治疗提供理论依据。方法：利用体内粒子植入模型研究^125I粒子持续低剂量率照射对前列腺癌PC-3移植瘤抑制作用。两颗粒子,线性排列,中间无间隔。每颗粒子活度1mCi。粒子植入后不同时间观察前列腺癌PC-3移植瘤体积变化和距离源中心层面不同垂直距离组织病理学变化。结果：^125I粒子组与假源粒子植入后不同时间测量肿瘤体积。^125I粒子组均有不同程度的抑制作用,其中粒子植入后96h实验组肿瘤抑制作用差异有统计学意义（P〈0．05）。组织病理学研究显示^125I粒子持续低剂量率照射不同时间后,距离粒子中心1．7mm处均有不同程度肿瘤细胞变性坏死,2．8mm处坏死区域明显减少,间质纤维化,增生明显。而空白对照组肿瘤细胞未见明显的变性坏死,周围亦无明显的纤维化。结论：^125I粒子持续低剂量率照射对前列腺癌PC-3移植瘤具有明显抑制作用,引起肿瘤组织变性坏死。