Morstyn G, Hsu S M, Kinsella T, Gratzner H, Russo A, Mitchell J B
J Clin Invest. 1983 Nov;72(5):1844-50. doi: 10.1172/JCI111145.
Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.
我们使用抗溴脱氧尿苷（BUdR）单克隆抗体和免疫组织化学方法，测定了这种胸腺嘧啶类似物在体内暴露的人正常细胞和恶性细胞DNA中的掺入情况。每天持续静脉输注BUdR 12或24小时，持续长达13天，输注期间稳态血浆水平为10⁻⁶ M。我们证明了BUdR广泛掺入正常皮肤、正常骨髓和恶性黑色素瘤细胞。此外，这种BUdR输注足以识别体内暴露的人骨髓染色体的姐妹染色单体交换。采用这种持续输注，观察到有明显但可逆的（急性）毒性，表现为骨髓抑制和皮肤光敏性。这些技术比使用胸腺嘧啶放射性同位素要简便得多，耗时也少得多，可用于对正常细胞和恶性细胞的细胞动力学及染色体复制进行进一步的人体研究。
