Measurement of the expected DNA lengthening caused by mono-and bisintercalating drugs using electron microscopy.

PM2 DNA molecules were treated with intercalating reagents (ethidium bromide, ethidium dimer, acridine dimer) and observed by electron microscopy. The adaptation of different electron microscopy techniques has enabled the determination of DNA lengthening upon drug intercalation. A 50% length increase was generally obtained for DNA saturated with the drugs. This result is in agreement with the intercalation model proposed by Lerman. In some cases (ethidium dimer), an increase of length larger than 50% can be obtained. Experimental conditions of DNA spreading strongly interfere with the DNA–drug interaction. In some cases it was possible to estimate the apparent binding constants and also to distinguish the mono- from the bisintercalating derivatives in their reaction with DNA.