DNA crosslinking by 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in HT-29 human colon carcinoma cells in vitro.

The Adriamycin analog, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin, is 100- to 1000-fold more active than Adriamycin as an antitumor agent in vivo and in vitro. The interaction of 3'-(3-cyano-4-morpholinyl)-3'deaminoadriamycin and Adriamycin with DNA has been studied in HT-29 human colon carcinoma cells in vitro. The Adriamycin analog produced significant DNA-DNA crosslinking at a drug concentration range that resulted in from 1 to 4 logs of cell kill, but did not produce any DNA-protein crosslinks. Equitoxic concentrations of Adriamycin produced no significant levels of DNA-DNA crosslinks. The formation of DNA-DNA crosslinks by the Adriamycin derivative is an additional mechanism of action that may account for the high potency of this agent.