Differential toxic effect of cis-platinum(II) and palladium(II) chlorides complexed with methyl 3,4-diamine-2,3,4,6-tetradeoxy-alpha-L-lyxo-hexopyranoside in mouse lymphoma cell lines differing in DSB and NER repair ability.

Abstract

The aim of this work was to test the cytotoxicity of newly synthesized cis-type complexes of platinum(II) and palladium(II) dichloride with methyl 3,4-diamine-2,3,4,6-tetradeoxy-alpha-L-lyxohexopyranoside, [M(C(7)H(16)N(2)O(2))Cl(2)].H(2)O, against two mouse lymphoma cell lines (L5178Y) differing in their double strand breaks and nucleotide excision repair ability. cis- Diaminedichloroplatinum (CDDP) was used as a reference compound. The toxicity of Pt(C(7)H(16)N(2)O(2))Cl(2) appeared to be similar for both cell lines: IC(50) is 8 microM for L5178Y-R cells and 12 microM for L5178Y-S cells, respectively. In contrast, the palladium complex was found to be more toxic for the LY-R cells than for the LY-S cells. The cytotoxicity of both compounds was compared with their ability to induce DNA crosslinks, as measured by the modified comet assay. CDDP caused retardation of the DNA migration induced by 2 Gy of the X-irradiation in a dose-dependent manner. The ability of Pd(C(7)H(16)N(2)O(2))Cl(2) to retard X-ray induced DNA migration was more pronounced than its platinum analogue and CDDP (see Fig. 6). However, this was not reflected in the toxicity of the compound. Such results indicate that these two compounds may cause a different type of DNA damage and/or that the DNA damage caused by the palladium(II) compound was dealt with in a different manner from that induced by the platinum(II) complex.