Residual radiation effect in the murine hematopoietic stem cell compartment

Stem cells surviving radiation injury may carry defects which contribute to long-term effects. The ratio of 125-iododeoxyuridine (IUdR) uptake into spleens of lethally irradiated recipient mice between day 3 and day 5 after cell transfusion revealed reduced proliferative ability (PF) of spleen seeding cells in parallel with reduced CFU-S content of donors throughout the study period of one year after 5 Gy gamma irradiation. Additional data aided in evaluating possible mechanisms of PF reduction. Within the range of the graft sizes used, PF was independent of the numbers of cells or CFU-S transfused. Radiation-induced increase in loss of label between days 3 and 5 and prolonged doubling time of proliferating cells indicated enhancement of cell maturation and increase in mitotic cycle time. Increased IUdR uptake per transfused CFU-S suggested extra divisions of transit cells due to insufficiency in the stem cell compartment. It is concluded that persisting defects in surviving stem cells interfere in a complex way with cell proliferation in the hemopoietic system.     

Cell loss from viable and necrotic tumour regions measured by 125I-UdR

Loss of cells from vital and necrotic areas of the syngeneic mammary adenocarcinoma EO 771 in male C57 BL/6J mice may be measured by use of 125I-labelled 5-iodo-2'-deoxyuridine (125I-UdR). Later than 50 hr after an intraperitoneal injection of 20 muCi 125I-UdR the incorporated activity of the entire tumour was externally measured and found to decrease with time after injection. The injected amount was neither chemo- nor radiotoxic. By injecting the vital dye 'light green', unstained necrotic and stained viable regions were separately excised and measured for loss of activity throughout the natural development of the labelled tumour. With the appearance of necrotic regions, labelled viable cells became necrotic, and activity was slowly eliminated. With increasing proportions of necrosis during tumour growth, the rate of loss of activity of the whole tumour decreased. Loss of activity from viable tumour regions reflected cell death and exceeded the loss rates of the whole tumour by a factor of 2 to 3. The data show that loss of activity from the whole tumour results from a superposition of different elimination rates of viable and necrotic tumour regions and is not an immediate consequence of cell death in the course of undisturbed tumour development.     

A microdosimetric understanding of low-dose radiation effects

This paper presents a microdosimetric approach to the problem of radiation response by which effects produced at low doses and dose rates can be understood as the consequences of radiation absorption events in the nucleus of a single relevant cell and in its DNA. Radiation absorption at the cellular level, i.e. in the cell nucleus as a whole, is believed to act through radicals. This kind of action is called 'non-specific' and leads to the definition of an 'elemental dose' and the 'integral response probability' of a cell population. Radiation absorption at the molecular level, i.e. in sensitive parts of the DNA, is thought to act through double-strand breaks. This kind of action is called 'specific' and leads to a 'relative local efficiency'. In general, both mechanisms occur for all types of radiation; however, it is the dose contribution of both specific and non-specific effects that determines the radiation quality of a given radiation. The implications of this approach for the specification of low-dose and low dose-rate regions are discussed.