CONVERSION OF MITOMYCIN-C TO 2,7-DIAMINOMITOSENE AND 10-DECARBAMOYL 2,7-DIAMINOMITOSENE IN TUMOR-TISSUE IN-VIVO

The progress of mitomycin C (MMC) bioreduction was studied in vivo in the rat Sp 107 mammary carcinoma after intra-tumoural injection of eit her 100 mu g or 1 mg. 2,7-Diaminomitosene (2,7-DM) was utilised as a p rimary bioreductive metabolite and 10-decarbamoyl 2,7-diaminomitosene (DC 2,7-DM) served as a secondary bioreductive metabolite, both of whi ch were measured by high-performance liquid chromatography. 2,7-DM and DC 2,7-DM were produced rapidly, achieving close to their maximal con centrations at the earliest time point studied [5 min]. 2,7-DM was cle ared rapidly from the tumour with apparent half-lives of 5 and 35 min after the low and high drug doses, respectively. DC 2,7-DM had a longe r apparent half-life of 130 min at the higher dose but, as compared wi th 2,7-DM, was only a minor metabolite [the area under the curve (AUC) of 2,7-DM was 5.6-fold that of DC 2,7-DM]. At the lower drug dose, DC 2,7-DM was not detectable. Rapid formation and disappearance of biore ductive metabolites of MMC may account for the failure of previous stu dies to detect these products in vivo.