Why the study?
Does razoxane alter daunomycin metabolism or its complexation with DNA in rat and mouse liver preparations and in vitro systems?
Does razoxane alter daunomycin metabolism or its complexation with DNA in rat and mouse liver preparations and in vitro systems?
Razoxane-protected daunomycin-induced toxicities in mice are likely not mediated through altered daunomycin metabolism or DNA complexation.
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Razoxane protection against daunomycin toxicity unlikely involves metabolism or DNA binding; leaves open alternative mechanisms for investigation in animal models.
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.
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Wang et al. (1980) studied this question.
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