Detectability in vivo of stabilized intercalating agents with the alkaline elution technique. Comparison with in vivo sister chromatid exchange introduction.
The purpose of the work reported here was to investigate, with the alkaline elution technique, the capability of in vivo administered actinomycin D, daunomycin and mitomycin C to induce DNA damage, DNA interstrand cross-linking and DNA-protein cross-linking. The ability of these compounds to induce increases in sister chromatid exchange (SCE) in the bone marrow cells of mice was also investigated. Actinomycin D and daunomycin were active in inducing single strands breaks, while mitomycin C was inactive. Mitomycin C showed a clear DNA interstrand cross-linking activity, while this activity was absent in actinomycin D and daunomycin. All three compounds were positive for SCE induction, but mitomycin C was by far the most active compound. Our results seem to suggest that stabilized intercalating agents are often detectable with the alkaline elution technique, after treatment in vivo. However, they cannot be evaluated with the simple alkaline elution technique only. It is convenient to add to the basic method the modification for detecting cross-links. Finally, DNA interstrand cross-linking and sister chromatid exchanges could be correlated.