Morphological transformation, DNA strand separation, and antinucleoside immunoreactivity following exposure of cells to intercalating drugs.
The intercalating drugs quinacrine and proflavine induced increases in single-stranded DNA detected in the nuclei of mouse BALB/c 3T3 1--13 cells. The denatured DNA was detected by fluorescein-labeled antinucleoside antibodies, which bind to single-stranded but not double-stranded DNA. Exposure of cells to the potent mutagen proflavine increased the fraction of immunoreactive nuclei from 0.65 to 0.8. With the weaker mutagen quinacrine, higher concentrations were needed to induce increases in immunoreactivity. Both intercalating drugs rapidly induced morphological transformation in mouse 3T3 cells. Treatment with proflavine resulted in higher transformation frequencies than were found with quinacrine. Significant increases in cell transformation frequency were observed at the concentrations which induced high levels of immunoreactivity. These results suggest that DNA strand separation is itself, or at least accompanies, an early step in cell transformation by intercalating drugs.
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007364:Intercalating Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009705:Nucleosides / Q000276:immunology; D011370:Proflavine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D007364:Intercalating Agents; D009705:Nucleosides; D004247:DNA; D011370:Proflavine; D011796:Quinacrine