Mitchell J B, Gamson J, Russo A, Friedman N, DeGraff W, Carmichael J, Glatstein E
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892.
NCI Monogr. 1988(6):187-91.
The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance.
将一种多药耐药的中国仓鼠卵巢多效细胞系(CHRC5)的内在细胞放射敏感性与其亲本细胞系(AuxB1)的进行了比较。CHRC5细胞系的辐射存活曲线参数n和D0分别为4.5和1.1 Gy,亲本细胞系的分别为5.0和1.2 Gy。因此,尽管采用谷胱甘肽、谷胱甘肽转移酶和过氧化氢酶的关键细胞内自由基清除和解毒系统在耐药细胞系中产生的酶水平分别高2.0倍、1.9倍和1.9倍,但这两种细胞系的内在放射敏感性相似。丁硫氨酸亚砜胺导致的谷胱甘肽耗竭在两种细胞系中引起相同程度的需氧放射增敏作用(约10%)。将碘脱氧尿苷掺入细胞DNA使两种细胞系对辐射敏感。这些研究表明,多药耐药不一定赋予放射抗性。