Lee S M, Harris M, Rennison J, McGown A, Bromley M, Elder R H, Rafferty J A, Crowther D, Margison G P
CRC Department of Medical Oncology, Christie Hospital (NHS) Trust, Manchester, U.K.
Eur J Cancer. 1993;29A(9):1306-12. doi: 10.1016/0959-8049(93)90079-u.
The cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens.
O6-烷基鸟嘌呤-DNA烷基转移酶（ATase）的细胞表达可能是决定肿瘤对某些烷化剂敏感性的一个重要因素。在一项比较研究中，我们使用兔抗人ATase抗血清，检测了一系列霍奇金病和卵巢癌患者肿瘤活检组织中ATase的细胞间和细胞内分布。该抗体在一些卵巢肿瘤的无细胞提取物的蛋白质免疫印迹上识别ATase蛋白，这些卵巢肿瘤的ATase活性通过体外测定为20至420 fmol/mg蛋白质，并且ATase活性与蛋白质免疫印迹上条带的强度之间存在线性相关性（r = 0.993）。在所检测的所有卵巢肿瘤中均可见免疫组织化学染色，且局限于细胞核。这与霍奇金病组织形成对比，在霍奇金病组织中染色明显减少，且存在于细胞核和细胞质中。结果表明，在卵巢肿瘤中，对亚硝基脲化疗的普遍耐药性可能与ATase蛋白的高细胞表达有关：这与对化疗更敏感的霍奇金病相反。这增加了通过对肿瘤或组织标本进行免疫组织化学染色来预测对这些烷化剂敏感性或耐药性的可能性。
