Kazuo T. Suzuki

Bio: Kazuo T. Suzuki is an academic researcher from Chiba University. The author has contributed to research in topics: Metallothionein & Cadmium. The author has an hindex of 41, co-authored 165 publications receiving 8791 citations. Previous affiliations of Kazuo T. Suzuki include National Institute for Environmental Studies & National Institute of Radiological Sciences.

Exposure, metabolism, and toxicity of rare earths and related compounds.

Abstract: For the past three decades, most attention in heavy metal toxicology has been paid to cadmium, mercury, lead, chromium, nickel, vanadium, and tin because these metals widely polluted the environment. However, with the development of new materials in the last decade, the need for toxicological studies on those new materials has been increasing. A group of rare earths (RE) is a good example. Although some RE have been used for superconductors, plastic magnets, and ceramics, few toxicological data are available compared to other heavy metals described above. Because chemical properties of RE are very similar, it is plausible that their binding affinities to biomolecules, metabolism, and toxicity in the living system are also very similar. In this report, we present an overview of the metabolism and health hazards of RE and related compounds, including our recent studies.

Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India.

Abstract: A speciation technique for arsenic has been developed using an anion-exchange high-performance liquid chromatography/inductively coupled argon plasma mass spectrometer (HPLC/ICP MS). Under optimized conditions, eight arsenic species [arsenocholine, arsenobetaine, dimethylarsinic acid (DMA(V)), dimethylarsinous acid (DMA(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), arsenite (As(III)), and arsenate (As(V))] can be separated with isocratic elution within 10 min. The detection limit of arsenic compounds was 0.14-0.33 microg/L. To validate the method, Standard Reference Material in freeze-dried urine, SRM-2670, containing both normal and elevated levels of arsenic was analyzed. The method was applied to determine arsenic species in urine samples from three arsenic-affected districts of West Bengal, India. Both DMA(III) and MMA(III) were detected directly (i.e., without any prechemical treatment) for the first time in the urine of some humans exposed to inorganic arsenic through their drinking water. Of 428 subjects, MMA(III) was found in 48% and DMA(III) in 72%. Our results indicate the following. (1) Since MMA(III) and DMA(III) are more toxic than inorganic arsenic, it is essential to re-evaluate the hypothesis that methylation is the detoxification pathway for inorganic arsenic. (2) Since MMA(V) reductase with glutathione (GSH) is responsible for conversion of MMA(V) to MMA(III) in vivo, is DMA(V) reductase with GSH responsible for conversion of DMA(V) to DMA(III) in vivo? (3) Since DMA(III) forms iron-dependent reactive oxygen species (ROS) which causes DNA damage in vivo, DMA(III) may be responsible for arsenic carcinogenesis in human.

Metabolomics of Selenium: Se Metabolites Based on Speciation Studies

Abstract: Selenium is a trace element essential for the normal function of the body. This metalloid is quite unique in its metabolism compared with typical essential metals such as copper and zinc. In the present communication, the metabolism of selenium in the body was reviewed from the viewpoint of metabolomics based on speciation studies. Both inorganic and organic forms of slenium can be the nutritional source, and they are transformed to the common intermediate, selenide or its equivalent. Selenite and selenate are reduced simply to selenide for further utilization and/or excretion. On the other hand, organic selenocysteine is directly lysed to selenide, while selenomethionine is transformed to selenocysteine (trans-selenation pathway), similarly to the trans-sulfuration pathway for methionine to cysteine, and then lysed to selenide. Selenide is known to be transformed to selenocysteine on tRNA, and the selenocysteinyl residue is incorporated into selenoprotein sequences by the codon specific to selenocysteine, UGA. Diverse selenium chemicals in foods seem to be recognized as selenium species and transformed to selenide, and then utilized for the synthesis of selenoproteins. Surplus selenium is methylated stepwise to methylated selenium metabolites from the common intermediate selenide. The major urinary metabolite is 1β-methylseleno-N-acetyl-D-galactosamine (selenosugar). Trimethylselenonium has been recognized as the urinary metabolite excreted in response to excessive doses and as a biological marker for excessive doses. However, recent results contradicted this.

Trivalent arsenicals are bound to proteins during reductive methylation.

Abstract: Inorganic arsenic is converted to methylated metabolites, and most is excreted in urine as dimethylarsinic acid in humans and animals. The present study was conducted to investigate the metabolism of arsenic and identify hepatic and renal metabolites of arsenic after an intravenous injection of arsenite (0.5 mg As/kg body weight) in rats. Similar levels of arsenic were found in the soluble (SUP) and nonsoluble sediment (SED) fractions of both organs after 1 h. More than 80% of the SUP arsenic was bound to high molecular weight (HMW) proteins in both organs. Arsenic bound to the HMW and SED proteins were oxidized with H2O2 and released in the pentavalent forms (arsenate, monomethylarsonic, and dimethylarsinic acids). The relative ratios of the three arsenicals changed depending on organ, fraction (HMW and SED), and time. Since the arsenic metabolites/intermediates were liberated from proteins by oxidation with H2O2 and recovered in the pentavalent forms, and only tri- but not pentavalent arsenicals were bo...

Polychlorinated Biphenyls (PCBs): Environmental Impact, Biochemical and Toxic Responses, and Implications for Risk Assessment

Abstract: Commercial polychlorinated biphenyls (PCBs) and environmental extracts contain complex mixtures of congeners that can be unequivocally identified and quantitated. Some PCB mixtures elicit a spectrum of biochemical and toxic responses in humans and laboratory animals and many of these effects resemble those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons, which act through the aryl hydrocarbon (Ah)-receptor signal transduction pathway. Structure-activity relationships developed for PCB congeners and metabolites have demonstrated that several structural classes of compounds exhibit diverse biochemical and toxic responses. Structure-toxicity studies suggest that the coplanar PCBs, namely, 3,3',4,4'-tetrachlorobiphenyl (tetraCB), 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, and their monoortho analogs are Ah-receptor agonists and contribute significantly to the toxicity of the PCB mixtures. Previous studies with TCDD and structurally related compounds ...