Effect of razoxane (ICRF 159) on daunomycin (NSC 82151) metabolism and DNA complexation

Daunomycinol and deoxyaglycone were the two major metabolites obtained from daunomycin in vitro metabolism by rat and mouse liver preparations. Pretreatment with razoxane (ICRF 159) in these animals did not appear to alter these major metabolic enzymes. In an in vitro system, it was found that daunomycin reacted with DNA instantly and reached steady states within two minutes as evidenced by the diminishing, shifting or disappearance of certain and visible regions. Preincubation of razoxane with DNA did not alter the latter's capacity to interact with daunomycin. We suggest that the mode of razoxane-protected daunomycin-induced toxicities in mice is not mediated through an alteration in daunomycin metabolism or its complexation with DNA.