Eldrige S R, Butterworth B E, Goldsworthy T L
Pathology Associates, Inc., Durham, NC 27713.
Environ Health Perspect. 1993 Dec;101 Suppl 5(Suppl 5):211-8. doi: 10.1289/ehp.93101s5211.
Two different markers for quantitating cell proliferation were evaluated in livers of control and chemically treated mice and rats. Proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, and bromodeoxyuridine (BrdU), an exogenously administered DNA precursor label, were detected in formalin-fixed, paraffin-embedded tissues using immunohistochemical techniques. The percentage of cells in S phase (labeling indexes, LI) evaluated as PCNA- or BrdU-positive hepatocellular nuclei was compared in recut tissue sections from animals given BrdU by a single IP injection 2 hr before killing the animals. Ten-week-old male B6C3F1 mice and F344 rats were exposed to known mitogenic hepatocarcinogens, Wy-14,643 (WY) in the diet at 0.1% for 2 days or 1,4-dichlorobenzene (DCB) in corn oil by gavage for 2 days (600 mg/kg/day in mice; 300 mg/kg/day in rats). In mice, PCNA and BrdU hepatocyte LI were similar in control, WY-treated, and DCB-treated animals. In rats, PCNA and BrdU gave similar LI in controls and Wy-treated animals. Although PCNA LI was statistically lower than BrdU LI in DCB-treated rats, both PCNA and BrdU LI for DCB-treated rats was increased over LI in control rats. Different patterns of PCNA immunohistochemical staining, interpreted to represent different subpopulations of cells at various phases of the cell cycle, were quantitated using PCNA immunohistochemistry. The proliferating index (PI), defined as the percentage of cells in the cell cycle (G1 + S + G2 + M), was more sensitive than the LI (S phase only) in detecting a chemically induced cell proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)
在对照小鼠和大鼠以及经化学处理的小鼠和大鼠的肝脏中，评估了两种用于定量细胞增殖的不同标志物。增殖细胞核抗原（PCNA）是一种内源性细胞复制标志物，而溴脱氧尿苷（BrdU）是一种外源性给予的DNA前体标记物，使用免疫组织化学技术在福尔马林固定、石蜡包埋的组织中进行检测。在处死动物前2小时通过单次腹腔注射给予BrdU的动物的重切组织切片中，比较了评估为PCNA或BrdU阳性肝细胞核的S期细胞百分比（标记指数，LI）。10周龄雄性B6C3F1小鼠和F344大鼠暴露于已知的促有丝分裂肝癌致癌物，饮食中含0.1%的Wy-14,643（WY），持续2天，或通过灌胃给予玉米油中的1,4-二氯苯（DCB），持续2天（小鼠600毫克/千克/天；大鼠300毫克/千克/天）。在小鼠中，对照、WY处理和DCB处理的动物中PCNA和BrdU肝细胞LI相似。在大鼠中，对照和Wy处理的动物中PCNA和BrdU的LI相似。虽然在DCB处理的大鼠中PCNA LI在统计学上低于BrdU LI，但DCB处理的大鼠中PCNA和BrdU LI均高于对照大鼠的LI。使用PCNA免疫组织化学对解释为代表细胞周期不同阶段不同细胞亚群的PCNA免疫组织化学染色的不同模式进行了定量。增殖指数（PI）定义为细胞周期（G1+S+G2+M）中的细胞百分比，在检测化学诱导的细胞增殖反应方面比LI（仅S期）更敏感。（摘要截断于250字）
