Hawkins Roland B
Radiation Oncology, Ochsner Medical Institutions, 1514 Jefferson Highway, New Orleans, LA 70121, USA.
Radiat Res. 2009 Dec;172(6):761-76. doi: 10.1667/RR1655.1.
The relationship between relative biological effectiveness in the limit of zero dose (RBE(1)) and the LET of radiation is examined and compared for several cell lines, including cells from patients with ataxia telangiectasia, in the context of a microdosimetric-kinetic (MK) model of cell killing by radiation. Evidence is presented that the sensitivity of a cell to low-LET photon radiation, as measured by the linear parameter of the linear-quadratic cell survival relationship (alpha), is largely determined by its vulnerability to formation of a lethal lesion from transformation of a single potentially lethal lesion (PLL) in DNA, as opposed to formation by combination of two PLL. As a result, the RBE(1) of cells that are relatively less sensitive to low-LET photon radiation increases more with increasing LET than the RBE(1) of cells that are more sensitive to low-LET radiation. As a consequence, a pair of cells that have clearly different sensitivity to low-LET radiation tend to have more nearly the same sensitivity as the LET increases into the range of 100 to 200 keV microm(-1). Cells with the same, or nearly the same, sensitivity to low-LET photon radiation continue to have nearly the same sensitivity as the LET is similarly increased. Thus there may be a radiobiological advantage to treatment with high-LET particle radiation for situations in which the target tumor cells are less radiosensitive than the cells that determine the tolerance of the normal tissue at risk. This may be the case for treatment of many of the common malignancies that occur in adults. This general principle may be helpful in selection of patients for treatment with particle radiation, such as carbon ions, and in the design of clinical trials to determine the optimal dose and fractionation schedules for such treatment.
在辐射致细胞死亡的微剂量动力学（MK）模型背景下，研究并比较了几种细胞系（包括共济失调毛细血管扩张症患者的细胞）在零剂量极限下的相对生物效应（RBE(1)）与辐射传能线密度（LET）之间的关系。有证据表明，通过线性二次细胞存活关系的线性参数（α）衡量的细胞对低LET光子辐射的敏感性，在很大程度上取决于其因DNA中单个潜在致死性损伤（PLL）转化形成致死性损伤的易感性，而非两个PLL组合形成致死性损伤的易感性。因此，对低LET光子辐射相对不敏感的细胞的RBE(1)随LET增加的增幅，大于对低LET辐射更敏感的细胞的RBE(1)增幅。结果，一对对低LET辐射敏感性明显不同的细胞，随着LET增加到100至200 keV µm⁻¹范围，其敏感性趋于更接近相同。对低LET光子辐射具有相同或几乎相同敏感性的细胞，随着LET以类似方式增加，其敏感性仍几乎相同。因此，对于靶肿瘤细胞比决定正常组织耐受剂量的细胞对辐射更不敏感的情况，用高LET粒子辐射治疗可能具有放射生物学优势。成人中发生的许多常见恶性肿瘤的治疗可能就是这种情况。这一普遍原则可能有助于选择接受粒子辐射（如碳离子）治疗的患者，并有助于设计临床试验以确定此类治疗的最佳剂量和分次方案。
