MEASUREMENT OF CHEMICALLY-INDUCED CELL-PROLIFERATION IN RODENT LIVER AND KIDNEY - A COMPARISON OF 5-BROMO-2'-DEOXYURIDINE AND [H-3] THYMIDINE ADMINISTERED BY INJECTION OR OSMOTIC PUMP
MEASUREMENT OF CHEMICALLY-INDUCED CELL-PROLIFERATION IN RODENT LIVER AND KIDNEY - A COMPARISON OF 5-BROMO-2'-DEOXYURIDINE AND [H-3] THYMIDINE ADMINISTERED BY INJECTION OR OSMOTIC PUMP
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DOI：
10.1093/carcin/11.12.2245
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发表时间：
1990-12-01
期刊：
影响因子：
4.7
通讯作者：
BUTTERWORTH, BE
中科院分区：
文献类型：
--
作者：
ELDRIDGE, SR;TILBURY, LF;BUTTERWORTH, BE
在对照和化学处理的小鼠和大鼠的肝脏和肾脏中，评估了不同的标记方法定量细胞增殖。用5-溴-2'-脱氧尿苷（BRDU）和[H-3]胸腺嘧啶分别比较动物组织中处于s期的细胞百分比（标记指数）。这些DNA前体标签在杀死动物前2小时通过单次静脉注射或通过sc植入的渗透泵传递3或6天。B6C3F1小鼠和雄性F344大鼠分别以0.1%的剂量暴露于过氧化物酶体增殖剂和肝癌致癌物WY - 14643 （WY）长达5天，或以玉米油中无基因毒性的小鼠肝脏和雄性大鼠肾脏致癌物1,4-二氯苯（DCB）灌胃长达5天（600 mg/kg/天）或长达3周（300 mg/kg/天，每周5天）。BRDU-和[H-3]胸腺嘧啶标记小鼠和大鼠肝脏和肾脏的标记指数（LIs）相似。与对照组相比，WY-和dcb处理的两种动物的肝脏细胞增殖都有所增加。经过4天的化学处理，在治疗的最后3天持续给予DNA前体标记物，对照组、DCB和wy处理的小鼠肝脏中BRDU的LIs分别为0.7、19%和17%，[H-3]胸苷的LIs分别为0.9、15%和13%。此外，BRDU和[H-3]胸腺嘧啶标记了相同的细胞群，这在处理动物的肝脏和肾脏中显示出相似的细胞标记模式。在DCB治疗4 d和DNA前体标记的最后3 d大鼠中，BRDU-和[H-3]胸腺嘧啶标记的肾近端小管细胞的LI分别为7.7和8.0%，而对照组的LI分别为4.3和3.7%。brdu标记大鼠经DCB治疗3周后，肾近端小管细胞LI增加至11%。在通过渗透泵接受DNA前体标记的对照组和处理动物中，肝脏和肾脏中的LIs最高，而在2小时脉冲标记的动物中最低。然而，在标记3天的处理动物中，肝脏LI的诱导作用最大。这些结果表明BRDU和[H-3]胸苷嘧啶标记方法对s期细胞的标记具有可比性。BRDU不存在放射性安全壳问题，并且比[H-3]胸苷更快地获得结果。在本研究中，BRDU在3天的渗透泵中被认为是评估化学诱导细胞增殖的首选方法。
Different labeling methods for quantitating cell proliferation were evaluated in livers and kidneys of control and chemically treated mice and rats. The percentage of cells in S-phase (labeling indices) were compared in tissues of animals given either 5-bromo-2'-deoxyuridine (BRDU) or [H-3]thymidine. These DNA precursor labels were delivered either by a single i.p. injection 2 h prior to killing the animals or via the s.c. implanted osmotic pump for 3 or 6 days. B6C3F1 mice and male F344 rats were exposed to either a peroxisome proliferator and hepatocarcinogen, Wy-14,643 (WY), in the diet at 0.1% for up to 5 days, or a non-genotoxic mouse liver and male rat kidney carcinogen, 1,4-dichlorobenzene (DCB), in corn oil by gavage for up to 5 days in mice (600 mg/kg/day) or up to 3 weeks in rats (300 mg/kg/day, 5 days per week). Labeling indices (LIs) in the liver and kidney were similar in BRDU- and [H-3]thymidine-labeled mice and rats. Cell proliferation was increased in the livers of both species of WY- and DCB-treated animals when compared to controls. After 4 days of chemical treatment with continuous administration of a DNA precursor label during the last 3 days of treatment, LIs in controls, DCB- and WY-treated mouse livers were 0.7, 19 and 17% for BRDU and 0.9, 15 and 13% for [H-3]thymidine respectively. Furthermore, BRDU and [H-3]thymidine labeled the same population of cells as revealed by similar patterns of cell labeling in the livers and kidneys of treated animals. The LI for BRDU- and [H-3]thymidine-labeled renal proximal tubular cells was 7.7 and 8.0% respectively, in rats receiving DCB for 4 days and DNA precursor label during the last 3 days of treatment, while the LI for controls was 4.3 and 3.7% respectively. The renal proximal tubular cell LI increased to 11% in BRDU-labeled rats treated with DCB for 3 weeks. LIs in both liver and kidney were greatest in control and treated animals that received the DNA precursor label via osmotic pumps for 6 days, and least in 2 h pulse-labeled animals. However, induction of hepatic LI in treated over control animals was greatest for treated animals labeled for 3 days. These results demonstrate comparable cell labeling of cells in S-phase with either BRDU and [H-3]thymidine labeling methods. BRDU presents no radioactive containment problems, and results are obtained more rapidly than [H-3]thymidine. In the present study, BRDU administered in a 3 day osmotic pump was judged to be the method of choice for assessing chemically induced cell proliferation.