Evaluation of side effects of platinum complexes (CDDP, CBDCA, CHIP) on rat bone marrow

The in vivo toxic actions of cis-dichloro-1, 1-cyclo-butane-dicarboxylate platinum (II): carboplatin (CBDCA), cis-diisopropyl-ammine-transdihydroxy-dichloro platinum (IV) and iproplatin (CHIP) were compared with those of cis-diamminedichloroplatinum (II): cisplatin (CDDP) on rat bone marrow. To elucidate the biochemical basis of side effects of platinum analogs, the protein and DNA content, thymidine kinase (TK) EC 2.7.1.21 activity and cellularity (MNC) were measured from the femoral bone marrow at 48 hours after i.v. single injection of these three compounds using equitoxic doses as fraction of LD50 (CDDP: 9, CHIP: 50, CBDCA: 80 mg/kg). Dose response studies showed that each drug depressed in dose dependent fashion the cellularity, DNA content and TK activity. As the I50 values indicated, the CHIP caused the most toxic effect in the bone marrow and the influence of CBDCA was the least. The nadir of biochemical alterations was observed 24-48 hours after drug administration. The recovery of bone marrow was completed 96 hours after the treatment.