Reference

Reaction of cis-diamminedichloroplatinum(II) and DNA in B or Z conformation

Reaction of cis-diamminedichloroplatinum(II) and DNA in B or Z conformation. Malinge, Jean Marc; Leng, Marc (Cent. Biophys. Mol., Orleans 45045, Fr.). EMBO J., 3(6), 1273-9 (English) 1984. CODEN: EMJODG. ISSN: 0261-4189. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The nature of the adducts and the conformational changes produced in poly(dG-m5dC).poly(dG-m5dC) by cis-diamminedichloroplatinum(II) (cisPt) [15663-27-1] have been studied. In the reaction of cisPt and B-DNA, the main adduct is bidentate and arises from an intrastrand cross-link between two guanine residues sepd. by a cytosine. The platinated polymer is not digested by S1 nuclease. The antibodies to Z-DNA bind to the platinated polymer with a smaller affinity than to poly(dG-br5dC).poly(dG-br5dC). The CD spectrum differs from that of poly(dG-br5dC).poly(dG-br5dC) or poly(dG-m5dC).poly(dG-m5dC) in Z conformation. Apparently, the bidentate adduct induces a conformational change from the B form towards a distorted Z form. In the reaction of cisPt and Z-DNA, a monodentate adduct is formed. This adduct stabilizes the Z conformation as shown by CD and binding to the anti-Z-DNA antibodies. At room temp., the second function of the drug can still react with small ligands such as NH4HCO3. By heating, the second function reacts with a guanine residue. A bidentate adduct is formed as in the reaction of cisPt and B-DNA and it induces a transition from the Z form to the distorted Z form.

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma. Berry, Jean Pierre; Pauwells, Catherine; Tlouzeau, Sylvie; Lespinats, Genevieve (Lab. Biophys., Fac. Med., Creteil 94010, Fr.). Cancer Res., 44(7), 2864-8 (English) 1984. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Fibrosarcoma-bearing mice were treated with a combination of cis-diamminedichloroplatinum(II) (cis-DDP) [15663-27-1] and Se. A dose of 2 or 4 mg Se/g had no effect on tumor growth. The i.p. injection of 16 mg cis-DDP/g led to early death of the animals. The i.p. treatment of tumor-bearing animals with 2 or 4 mg Se/g reduced the early mortality induced by cis-DDP at 16 mg/g. Therefore, the addn. of Se allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect. Clonogenic assays following drug exposure showed that Se had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Reduced ultrastructural changes in renal cells were obsd. when Se was added to the cis-DDP treatment. Microanal. showed no accumulation of either Se or Pt within renal cells. Apparently, the addn. of Se decreases the nephrotoxicity of cis-DDP.