Mitoxantrone and ametantrone induce interstrand cross-links in DNA of tumour cells

Abstract

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 crosslinking is associated with the cytotoxic and anti-tumour activity of these compounds. (C) 2000 Cancer Research Campaign.