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Platinum tetrachloride: mutagenicity and methylation with methylcobalamin

Journal Article · · J. Environ. Sci. Health, Part A; (United States)
It was reported earlier that methylcobalamin (MeB-12) plus K/sub 2/PtCl/sub 6/ or Na/sub 2/PtCl/sub 6/ under acidic conditions yields a single square planar Pt/sup 2 +/ species, MePtCl/sub 3//sup 2 -/. A reaction between MeB-12 and PtCl, in H/sub 2/O has now been shown to occur. Complete demethylation requires two equivalents of PtCl/sub 4/ and MePtCl/sub 3//sup 2 -/ 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 MePtCl/sub 3//sup 2 -/ 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(H/sub 2/O)Cl/sub 2//sup 1 -/ (pKa ca. 4.5). A linear bridged intermediate is proposed to account for the methylation products obtained from MeB-12 and K/sub 2/PtCl/sub 6/ (or PtCl/sub 4/) and the catalytic role of K/sub 2/PtCl/sub 4/. As part of a systematic study of Pt-complex mutagenesis, we also report quantitative data on the cytotoxicity and mutagenicity of PtCl/sub 4/ in two closely related Chinese hamster ovary lines, CHO-S and CHO-AUXB1. In CHO-S cells PtCl/sub 4/ induces forward mutations to 8-azaguanine resistance/hypoxanthine-guanine phosphoribosyl transferase locus (8-AG/sup R//HGPRT locus), but not to ouabain resistance (OUA/sup R/). It also induces the reversion of CHO AUXB1, a triple auxotroph. The mutagenic effects of PtCl/sub 4/ in both CHO lines are dose dependent in the 5-30 ..mu..M concentration range.
Research Organization:
Univ. of California, Livermore
OSTI ID:
5366858
Journal Information:
J. Environ. Sci. Health, Part A; (United States), Journal Name: J. Environ. Sci. Health, Part A; (United States) Vol. 14:2; ISSN JESED
Country of Publication:
United States
Language:
English