Electron microscopic observations of the effects of anthraquinone derivatives on plasmid DNA.
Electron microscopy was used to analyse the precipitation of DNA observed when mixed with two tripeptide derivatives of mitoxantrone, with or without a 5,8-dihydroxy group (DHQ-GHK and Q-GHK, respectively) on the anthraquinonic ring. This precipitation was compared to that obtained with the basic drugs, mitoxantrone (DHAQ) and ametantrone (AQ). The effects of these compounds on the supercoiling of form I and the lengthening of form II of pBR322 DNA molecules, respectively, were evaluated. A strong lengthening of the DNA molecules was observed for ametantrone (max: 57%), but only 32% for Q-GHK, both at r (drug/base pari) = 250. With the dihydroxy derivative DHQ-GHK, it was not possible to show more than a 10% increase in length because DNA molecules were not measurable at r greater than 100. Only Q-GHK relaxed supercoiled molecules at the low r values of 10. Complex phenomena of condensation-precipitation were observed with these two tripeptide derivatives. In addition to a strong lengthening of form II DNA molecules, AQ induced specifically the formation of toruses, and DHAQ that of large organized DNA condensation. The variety of the aggregations is described and discussed with regard to the antitumor properties of these derivatives, and the literature concerning the various descriptions of DNA aggregation.
Morier-Teissier
E
E
Unité INSERM No 16, CHR Place de Verdun, Lille, France.
Bernier
J L
JL
Coulaud
D
D
Hénichart
J P
JP
Delain
E
E
D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D011232:Chemical Precipitation; D004278:DNA, Superhelical / Q000187:drug effects* / Q000648:ultrastructure; D007364:Intercalating Agents / Q000494:pharmacology*; D008854:Microscopy, Electron; D008942:Mitoxantrone / Q000031:analogs & derivatives / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D010957:Plasmids / Q000187:drug effects / Q000235:genetics
D000880:Anthraquinones; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D007364:Intercalating Agents; C075335:4-(glycyl-histidyl-lysine)-1-hydroxyanthraquinone; C075336:4-(glycyl-histidyl-lysine)-1,5,8-trihydroxyanthraquinone; D008942:Mitoxantrone; C020182:ametantrone