CROSS-LINKING AND SEQUENCE-SPECIFIC ALKYLATION OF DNA BY AZIRIDINYLQUINONES .1.. QUINONE METHIDES

The cytotoxicities and DNA cross-linking abilities of 16 1,4-benzoquin ones have been investigated. All of the alkylmonoaziridinyl-1,4-benzoq uinones were able to interstrand crosslink DNA after reduction and wer e cytotoxic in vitro. Compounds lacking an aziridine group were unable to cross-link DNA and were less cytotoxic. The methyl analogues were shown to preferentially react at <T(G)under bar C> sequences. From com paring the structural requirements for crosslinking and the cytotoxici ties, a mechanism has been proposed wherein some hydroquinones can ass ociate and react at <T(G)under bar C> sequences in DNA. These hydroqui nones can subsequently autoxidize to form a reactive quinone methide w hich reacts at the opposite strand to form a cross-link.