Mitoxantrone and ametantrone induce interstrand cross-links in DNA of tumour cells.
We show here that mitoxantrone and ametantrone induce interstrand DNA cross-links in HeLa S3 cells. These cross-links were observed only in cellular system suggesting that metabolism of the drugs is a necessary step leading to DNA cross-linking. Biologically inactive analogue of mitoxantrone, compound NSC 321458, did not induce cross-links in DNA of tumour cells which suggests that DNA cross-linking is associated with the cytotoxic and anti-tumour activity of these compounds.
Skladanowski
A
A
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdanśk, Poland.
Konopa
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D008942:Mitoxantrone; C020182:ametantrone