Platinum tetrachloride: Mutagenicity and methylation with methylcobalamin
Titel:
Platinum tetrachloride: Mutagenicity and methylation with methylcobalamin
Auteur:
Taylor, Robert T. Happe, James A. Hanna, M. Leslie Wu, Rebekah
Verschenen in:
Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering
Paginering:
Jaargang 14 (1979) nr. 2 pagina's 87-109
Jaar:
1979
Inhoud:
It was reported earlier that methylcobalamin (MeB-12) plus K2PtCl6 or Na2PtCl6 under acidic conditions yields a single square planar Pt2+ species, MePtCl2-3. A reaction between MeB-12 and PtCl4 in H2O has now been shown to occur. Complete demethylation requires two equivalents of PtCl4 and MePtCl2-3 is the principal product. In addition, a second Me-Pt product has been detected and isolated. It has a Me/Pt ratio of 1.0, but it lacks the 260 nm absorption maximum of MePtCl2-3 and it has a lower electrophoretic mobility at pH 4.5. The proton NMR spectrum of this product shows a typical triplet pattern, but the chemical shift of the center band and the spin coupling constant change with pH. Its NMR parameters suggest that this species is MePt(H2O)Cl1-2 (pKa ca. 4.5). A linear bridged intermediate is proposed to account for the methylation products obtained from MeB-12 and K2PtCl6 (or PtCl4) and the catalytic role of K2PtCl4. As part of a systematic study of Pt-complex mutagenesis, we also report quantitative data on the cytotoxicity and mutagenicity of PtCl4 in two closely related Chinese hamster ovary lines, CHO-S and CHO-AUXB1. In CHO-S cells PtCl4 induces forward mutations to 8-azaguanine resistance/hypoxanthine-guanine phosphoribosyl transferase locus (8-AGR/HGPRT locus), but not to ouabain resistance (OUAR). It also induces the reversion of CHO AUXB1, a triple auxotroph. The mutagenic effects of PtCl4 in both CHO lines are dose dependent in the 5-30 μM concentration range.