Lanier T L, Berger E K, Eacho P I
Department of Biochemical Toxicology, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140.
Carcinogenesis. 1989 Jul;10(7):1341-3. doi: 10.1093/carcin/10.7.1341.
Hepatocyte replication traditionally has been studied by [3H]thymidine (TdR) incorporation into DNA, and more recently using incorporation of 5-bromo-2-deoxyuridine (BUdR), a synthetic analog of thymidine which is measured by immunohistochemistry. In studies to compare TdR and BUdR, mice were given the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14643) in the diet (0.1%) for 5 days and either TdR (1 microCi/g) or BUdR (100 mg/kg) on days 2-5. The labeling index (LI) for hepatocytes of WY-14643-treated mice was 4.7% with BUdR and 5.2% with TdR. The LI for control mice was 0.3-0.4% with either label. Partially hepatectomized rats given TdR had a mean LI of 30.0 versus 32.0% in rats labeled with BUdR. Sham-operated controls given TdR had a mean LI of 0.2% and BUdR controls had a mean LI of 0.1%. Hepatectomized rats given TdR and BUdR simultaneously had an LI of 20.1% for TdR and 22.4% for BUdR. In these rats, 94.1% of the labeled cells contained both markers, whereas 1.9% had only TdR and 4.0% had only BUdR. Comparable labeling indices using either TdR or BUdR indicate that the analogs may be used interchangeably in short-term in vivo studies of liver cell proliferation.
传统上，肝细胞复制是通过将[3H]胸腺嘧啶核苷（TdR）掺入DNA来研究的，最近则是使用5-溴-2-脱氧尿苷（BUdR）掺入法，BUdR是胸腺嘧啶核苷的一种合成类似物，通过免疫组织化学进行检测。在比较TdR和BUdR的研究中，给小鼠喂食含过氧化物酶体增殖剂[4-氯-6-(2,3-二甲苯胺基)-2-嘧啶基硫代]乙酸（WY-14643）的饲料（0.1%），持续5天，并在第2至5天给予TdR（1微居里/克）或BUdR（100毫克/千克）。用BUdR处理的WY-14643小鼠肝细胞标记指数（LI）为4.7%，用TdR处理的为5.2%。对照小鼠使用任何一种标记物的LI均为0.3 - 0.4%。接受TdR的部分肝切除大鼠的平均LI为30.0%，而接受BUdR标记的大鼠为32.0%。接受TdR的假手术对照大鼠的平均LI为0.2%，接受BUdR的对照大鼠的平均LI为0.1%。同时接受TdR和BUdR的肝切除大鼠，TdR的LI为20.1%，BUdR的LI为22.4%。在这些大鼠中，94.1%的标记细胞同时含有两种标记物，而1.9%仅含有TdR，4.0%仅含有BUdR。使用TdR或BUdR得到的可比标记指数表明，在肝细胞增殖的短期体内研究中，这些类似物可以互换使用。
