Brambilla G, Carlo P, Marinari U
Toxicol Pathol. 1984;12(3):291-4. doi: 10.1177/019262338401200314.
Basic requirements for a method used to study the genotoxic potential of xenobiotic agents in the intact animal are sensitivity and capability of detecting the effect of the compound under test in various tissues. A new viscometric technique, which has been found capable of measuring DNA damage in liver, kidney, and lung of rats treated with small single doses of 10 chemical carcinogens, seems to possess such requirements. Single-strand breaks and probably other types of lesions indeed cause changes in DNA supercoiling which can be sensitively measured by monitoring time-dependent changes of DNA viscosity. The main advantage of this technique is that clear-cut modifications of viscometric parameters can be obtained with doses of various carcinogens markedly lower than those found to be the minimal effective ones in other commonly employed short-term in vivo tests. The importance of studying the genotoxic effects of pharmacologically meaningful doses is discussed.
用于研究完整动物体内外源性物质遗传毒性潜力的方法的基本要求是灵敏度以及检测受试化合物在各种组织中的效应的能力。一种新的粘度测定技术，已发现它能够测量用小单剂量的10种化学致癌物处理的大鼠肝脏、肾脏和肺中的DNA损伤，似乎具备这些要求。单链断裂以及可能的其他类型损伤确实会导致DNA超螺旋发生变化，这可以通过监测DNA粘度随时间的变化来灵敏地测量。该技术的主要优点是，使用各种致癌物的剂量明显低于其他常用短期体内试验中发现的最小有效剂量，就可以获得粘度测定参数的明确改变。文中讨论了研究药理学上有意义剂量的遗传毒性效应的重要性。
