Feinendegen L E, Cronkite E P
Curr Top Radiat Res Q. 1978 Jan;12(1-4):83-99.
The heterogeneous distribution and accumulation of radionuclides in discrete areas of cellular and subcellular dimensions is called microdistribution. The biological effect of microdistributed radionuclides with low-range emissions is determined by the degree of irradiation of the radiosensitive microareas of the body. The critical microareas of the body are nuclei of such cells which (1) are radiosensitive, (2) are essential to maintaining life, (3) are irreplaceable, (4) have a long life span and/or renew themselves. In this sense, the stem cell nuclei are considered critical microareas of the body. Stem cells constitute only a small fraction of the total body's cellularity. In case of concentration of radionuclides in stem cell nuclei, such as from incorporated labeled DNA precursors, there is a total congruence of the radionuclide microdistribution with the radiosensitive microarea, and the biological effect is expected to be enhanced over that from a homogeneous distribution of the same amount of radionuclides. This situation is discussed for 3H, 14C and 125I incorporate into mice as tracers of DNA precursors. The average labeling intensity of the bone marrow cell nucleus was taken to represent the average labeling intensity of the stem cell nucleus. The dose to the stem cell nucleus, then, is derived from the number and energy of decays originating in the nuclear mass of 270 X 10(-12) g. The transmutation effect from isotopic decay in DNA is considered in order to arrive at dose equivalents. On the basis of known data on labeling efficiency of bone marrow and on stem cell proliferation kinetics in the mouse, the infinite accumulation of decays in and the total expected dose to the stem cell nucleus was calculated for intravenous injection or ingestion of 1 muCi 3H-TdR per g body weight. The distribution factor and an annual limit on intake for the mouse model was suggested. Corresponding data are presented for 14C-TdR and 125I-UdR. A special situation is given for the case of hot particles where there is a random relationship between microdistributed radionuclides and critical microareas of the body. In this instance, theory predicts a decreased biological effect in comparison to the situation where the same amount of radionuclides is homogeneously distributed. There is experimental evidence that supports the theoretical predictions particularly for the case of 236Pu dioxide in the human lung.
放射性核素在细胞和亚细胞尺度的离散区域内的非均匀分布和积累被称为微观分布。具有低射程发射的微观分布放射性核素的生物学效应取决于机体放射敏感微观区域的辐照程度。机体的关键微观区域是这样一些细胞的细胞核,这些细胞:(1)对辐射敏感;(2)对维持生命至关重要;(3)不可替代;(4)寿命长和/或能够自我更新。从这个意义上讲,干细胞核被认为是机体的关键微观区域。干细胞仅占机体细胞总数的一小部分。如果放射性核素在干细胞核中浓集,例如来自掺入的标记DNA前体,那么放射性核素的微观分布与放射敏感微观区域完全一致,并且预期其生物学效应会比相同量的放射性核素均匀分布时增强。本文针对作为DNA前体示踪剂的3H、14C和125I掺入小鼠体内的情况进行了讨论。骨髓细胞核的平均标记强度被用来代表干细胞核的平均标记强度。然后,干细胞核的剂量由源自270×10⁻¹²g核质量的衰变数量和能量得出。为了得出剂量当量,考虑了DNA中同位素衰变的嬗变效应。根据已知的小鼠骨髓标记效率数据和干细胞增殖动力学,计算了每克体重静脉注射或摄入1μCi 3H - TdR时干细胞核内衰变的无限积累和总预期剂量。提出了小鼠模型的分布因子和年摄入量限值。给出了14C - TdR和125I - UdR的相应数据。对于热粒子的情况给出了一种特殊情形,即微观分布的放射性核素与机体的关键微观区域之间存在随机关系。在这种情况下,理论预测与相同量的放射性核素均匀分布的情况相比,生物学效应会降低。有实验证据支持这些理论预测,特别是对于人体肺部二氧化钚236Pu的情况。