SummaryPersistent left superior vena cava (PLSVC) is the most common congenital malformation of thoracic venous return and is present in 0.3 to 0.5% of individuals in the general population. This heart specimen was dissected from a 35-yearold male cadaver whose cause of death was determined as non-cardiac. The heart was examined and we found a PLSVC draining into the coronary sinus. The right superior vena cava was present with a small-diameter ostium. An anomalous pulmonary vein pattern was observed; there was a common trunk to the left superior and left inferior pulmonary veins (diameter 17.8 mm) and an additional middle right pulmonary vein (diameter 2.7 mm) with two classic right pulmonary veins. The PLSVC draining into the coronary sinus had led to its enlargement, which could have altered the cardiac haemodynamics by significantly reducing the size of the left atrium and impeding its outflow via the mitral valve.
Arsenic compounds are human carcinogens. The ingested inorganic arsenic is metabolized to methylated derivatives, which are considered to be more toxic than the inorganic species. Interactions of trivalent arsenicals with thiol groups of proteins are believed to be important for arsenic carcinogenesis, but inorganic arsenite appears to bind to thiol groups more strongly than the methylated As (III) species. Inhibition of the nucleotide excision repair pathway of DNA repair (NER) is likely to be of primary importance in arsenic carcinogenesis. Previously, we demonstrated that methylated As (III) compounds are more efficient than arsenite in releasing zinc from ZnXPAzf, the zinc finger of XPA, a crucial member of the NER complex [Schwerdtle, T., Walter, I., and Hartwig, A. (2003) Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and Fpg. DNA Repair (Amsterdam) 2, 1449-1463]. In this work, we used ESI-MS to compare aerobic reactivities of arsenite and monomethylarsonous acid (MMA (III)) toward ZnXPAzf on the molecular level. We demonstrated that equimolar MMA (III) released Zn (II) from ZnXPAzf easily, forming mono- and diarsenical derivatives of XPAzf. This reaction was accompanied by oxidation of unprotected thiol groups of the monomethylarsinated peptide to intramolecular disulfides. The estimated affinity of MMA (III) to XPAzf is 30-fold higher than that established previously for arsenite binding to the thiol groups. No binding of arsenite to the thiol groups of XPAzf was observed under our experimental conditions, and a 10-fold excess of arsenite was required to partially oxidize ZnXPAzf. These results indicate a particular susceptibility of tetrathiolate zinc fingers to MMA (III), thereby providing a novel molecular pathway in arsenic carcinogenesis.
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