The Usefulness of Viscometric Analysis for Detecting Minimal Levels of DNA Fragmentation

Abstract

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.