Arteel G E, Thurman R G, Yates J M, Raleigh J A
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Br J Cancer. 1995 Oct;72(4):889-95. doi: 10.1038/bjc.1995.429.
Nitroimidazole markers of tumour hypoxia bind to normoxic liver and the question has been raised whether this is due to low oxygen concentration or microregional activity of specialised nitroreductases. To answer this question, the binding patterns of the 2-nitroimidazole, pimonidazole, were compared following perfusion of surgically isolated rat livers in anterograde and retrograde directions. Perfusion at low flow rates in anterograde or retrograde directions can be used intentionally to alter oxygen gradients without altering enzyme distributions. Perfusion by means of the portal vein (anterograde direction) produced pimonidazole binding in the pericentral region of liver similar to that observed for pimonidazole binding in vivo. A complete reversal of this binding pattern occurred when the isolated liver was perfused by way of the central vein (retrograde direction). In this case, pimonidazole binding occurred in the periportal region. The extent and intensity of binding in the periportal region during perfusion in the retrograde direction was similar to that in the pericentral region during perfusion in the anterograde direction. It is concluded that low oxygen concentration rather than the non-homogeneous distribution of nitroreductase activity is the primary determinant of 2-nitroimidazole binding in liver.
肿瘤缺氧的硝基咪唑标记物会与正常氧合的肝脏结合，于是有人提出这是否是由于低氧浓度或特殊硝基还原酶的微区活性所致。为回答这个问题，在对手术分离的大鼠肝脏进行顺行和逆行灌注后，比较了2-硝基咪唑匹莫硝唑的结合模式。顺行或逆行低流速灌注可有意用于改变氧梯度而不改变酶的分布。通过门静脉灌注（顺行方向）在肝脏中央周围区域产生的匹莫硝唑结合与体内观察到的匹莫硝唑结合相似。当通过中央静脉灌注分离的肝脏（逆行方向）时，这种结合模式完全逆转。在这种情况下，匹莫硝唑结合发生在门静脉周围区域。逆行灌注期间门静脉周围区域的结合程度和强度与顺行灌注期间中央周围区域的相似。结论是，低氧浓度而非硝基还原酶活性的不均匀分布是肝脏中2-硝基咪唑结合的主要决定因素。
