Leung S W, Mitchell J B, al-Nabulsi I, Friedman N, Newsome J, Belldegrun A, Kasid U
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University, Washington, DC 20007.
Cancer. 1993 Apr 1;71(7):2276-85. doi: 10.1002/1097-0142(19930401)71:7<2276::aid-cncr2820710718>3.0.co;2-7.
Renal cell carcinoma (RCC) is a progressive and relatively radioresistant disease. Currently, no data are available on the in vitro radiobiologic characterization of renal tumor cells to the authors' knowledge.
Two RCC were cultured from specimens from previously untreated patients after either surgical resection of the primary tumor or from the malignant ascites. These two cell lines were characterized with respect to cytogenetic abnormalities, gamma radiation survival response, intracellular levels of glutathione and its related detoxification enzymes, and the effect of glutathione depletion on radiation toxicity.
The two RCC grew as adherent monolayer cultures with a median doubling time of 29 hours and 37 hours, respectively. Histopathologic analysis of the tumor cells grown in the renal capsule of the athymic mice confirmed their epithelial neoplastic growth. Both cell lines were aneuploid (range, 65-100 chromosomes) and had several marker chromosomes, including those derived from chromosomes 3, 7, and 11. In vitro radiation survival analysis indicated the relative radioresistance (RR; Do, 2.35 Gy) and relative radiosensitivity (RS; Do, 1.42 Gy), respectively, of these tumor cell lines. The levels of intracellular glutathione (GSH) were higher in the RR cells compared with the RS cells. The enzymatic activities of GSH S-transferase, GSH reductase, and the levels of GSH peroxidase and superoxide dismutase were elevated in the RS cells compared with the RR cells. L-Buthionine sulfoximine (BSO) treatment (concentration, 20 microM, applied for 17 hours) resulted in 77% and 63% GSH depletion compared with the untreated RR and RS cells, respectively. Pretreatment with higher concentration of BSO (50 microM for 17 hours) caused a modest radiosensitization of the RR cells (Do, 1.78 Gy).
RCC have a differential pattern of radiosensitivity. BSO treatment causes moderate radiosensitization of the relatively radioresistant renal tumor cells.
肾细胞癌（RCC）是一种进行性且相对放射抗拒的疾病。据作者所知，目前尚无关于肾肿瘤细胞体外放射生物学特征的数据。
从先前未经治疗的患者标本中培养出两株肾细胞癌，这些标本来自原发性肿瘤手术切除后或恶性腹水。对这两株细胞系进行细胞遗传学异常、γ射线辐射存活反应、细胞内谷胱甘肽及其相关解毒酶水平以及谷胱甘肽耗竭对辐射毒性的影响等方面的特征分析。
这两株肾细胞癌以贴壁单层培养方式生长，中位倍增时间分别为29小时和37小时。对在无胸腺小鼠肾包膜中生长的肿瘤细胞进行组织病理学分析，证实了其上皮性肿瘤生长。两株细胞系均为非整倍体（范围为65 - 100条染色体），并有几条标记染色体，包括源自3号、7号和11号染色体的染色体。体外辐射存活分析分别表明这些肿瘤细胞系的相对放射抗拒性（RR；Do，2.35 Gy）和相对放射敏感性（RS；Do，1.42 Gy）。与RS细胞相比，RR细胞内谷胱甘肽（GSH）水平更高。与RR细胞相比，RS细胞中谷胱甘肽S - 转移酶、谷胱甘肽还原酶的酶活性以及谷胱甘肽过氧化物酶和超氧化物歧化酶水平升高。与未处理的RR和RS细胞相比，L - 丁硫氨酸亚砜胺（BSO）处理（浓度为20μM，作用17小时）分别导致GSH耗竭77%和63%。用更高浓度的BSO（50μM作用17小时）预处理使RR细胞产生适度的放射增敏作用（Do，1.78 Gy）。
肾细胞癌具有不同的放射敏感性模式。BSO处理可使相对放射抗拒的肾肿瘤细胞产生适度的放射增敏作用。
