Livingston D M, Ferguson C, Gollogly R, Lazarus H
Cell. 1976 Jan;7(1):41-7. doi: 10.1016/0092-8674(76)90253-1.
Certain continuous lymphoid and myeloid tumor cell lines of rodent origin are unable to grow in tissue culture in the absence of pre-formed L-cystine (CYS). In contrast, three NZB murine lymphoid cell lines obtained from NZB mice free of hematopoietic neoplasm can grow as well in cystine-deficient media containing L-cystathionine (CSN), the immediate precursor of CYS in the biosynthetic pathway, as in cystine sufficient medium. The former class of cells is, therefore, CYS auxotrophs (CYS-) and the latter CYS prototrophs (CYS+). Compared to CYS+ cells, the CYS- lines appear to be relatively deficient in the enzyme cystathionase, which catalyzes the cleavage of CSN to CYS and alpha-ketobutyrate. Using protein synthetic capacity as a criterion, normal thymocytes from mixed-bred Swiss mice behave like CYS prototrophs, while those from littermates bearing Moloney type C virus-induced thymic tumors behave like CYS auxotrophs. The former are also characterized by substantially higher levels of cystathionase than the latter. Extracts of thymocytes from tumor-free AKR mouse thymus are also characterized by higher levels of cystathionase activity than extracts of spontaneous AKR thymomas. Exogenous in vitro type C virus infection of a CYS+ cell results in vigorous virus production but no concomitant reduction in cystathionase activity. Thus viral replication alone in any random lymphoid cell is not sufficient to alter the enzyme level. The data therefore suggests that CYS auxotrophy may closely accompany neoplastic transformation of certain hematopoietic cells in vivo, including that induced by certain "thymic" type C viruses.
某些源自啮齿动物的连续淋巴细胞和髓细胞肿瘤细胞系，在没有预先形成的L-胱氨酸（CYS）的情况下无法在组织培养中生长。相比之下，从无造血肿瘤的NZB小鼠获得的三种NZB鼠淋巴细胞系，在含有L-胱硫醚（CSN，生物合成途径中CYS的直接前体）的胱氨酸缺陷培养基中，与在胱氨酸充足的培养基中一样能够良好生长。因此，前一类细胞是CYS营养缺陷型（CYS-），而后一类是CYS原养型（CYS+）。与CYS+细胞相比，CYS-细胞系似乎相对缺乏催化CSN裂解为CYS和α-酮丁酸的胱硫醚酶。以蛋白质合成能力为标准，杂种瑞士小鼠的正常胸腺细胞表现得像CYS原养型，而携带莫洛尼C型病毒诱导的胸腺肿瘤的同窝小鼠的胸腺细胞则表现得像CYS营养缺陷型。前者的胱硫醚酶水平也明显高于后者。无肿瘤的AKR小鼠胸腺细胞提取物的胱硫醚酶活性水平也高于自发AKR胸腺瘤的提取物。CYS+细胞的体外C型病毒感染会导致大量病毒产生，但胱硫醚酶活性不会随之降低。因此，在任何随机淋巴细胞中仅病毒复制不足以改变酶水平。因此，数据表明CYS营养缺陷可能与体内某些造血细胞的肿瘤转化密切相关，包括某些“胸腺”型C病毒诱导的肿瘤转化。
