Study of Germanium Dioxide : Subcellular Distribution and Chronic Toxicity

Research Project

Project/Area Number	04670304
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Hygiene
Research Institution	University of Tokyo
Principal Investigator	YAMAZAKI Nobuyuki University of Tokyo, Faculty of Medicine, Department of Hygiene and Preventive Medicine Technical Official, Ministry of Education, 医学部(医), 教務職員 (40143424)
Co-Investigator(Kenkyū-buntansha)	WADA Osamu University of Tokyo, Faculty of Medicine, Department of Hygiene and Preventive M, 医学部(医), 教授 (60009933)
Project Period (FY)	1992 – 1993
Project Status	Completed (Fiscal Year 1993)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords	Germanium dioxide / Kidney / Distribution / Chronic toxicity / Subcellular fractionation / Urine / ゲルマニウム / 腎機能障害
Research Abstract	To clarify the biological effects of germanium dioxide (GeO_2) on kidney, we investigated the subcellular distribution and the chronic toxicity of GeO_2 on rats. The following results were obtained. 1. Germanium distribution in the subcellular fractions of rat kidney. A single dose of a GeO_2 was intraperitoneally administered to rats (50mg Ge/kg bw), and the subcellular distribution of GeO_2 in kidney was measured from 30 minutes to 24 hours after dosing. In kidney, GeO_2 showed the highest concentration at 30 minutes, and decreased rapidly. The half life of GeO_2 in the tissue was approximately 10 hours. The reduction of the GeO_2 contents in each subcellular fraction was fast, too. But the relative GeO_2 contents among subcellular fractions changed little by the time after dosing. More than two third of GeO_2 distributed in the cytosolic fractions (Nuclear fr.12-14%, Mitochondrial fr.10-15%, Microsomal fr.2-7%, Cytosolic fr.65-76%). The GeO_2 contents per protein weight were also highest in the cytosolic fractions. At 6 hours, the concentrations of Ge (mug Ge/100mg protein) in nuclear fr.mitochondrial fr., microsomal fr.and cytosolic fr.were 2.32(〕SY.+-.〔)1.08, 2.80(〕SY.+-.〔)1.19, 1.15(〕SY.+-.〔)0.47 and 9.94(〕SY.+-.〔)4.45, respectively. 2. Chronic toxicity of GeO_2 on rats. GeO_2 (25mg Ge/kg bw, 5mg Ge/kg bw) or saline (control group) was administered subcutaneously to rats for 13 weeks. No change of general appearance and behavior of animals was observed. First 5 weeks, the body weight gains of GeO_2 groups were less than control group, but tose were not significant. There were the increase of urinary volume and the decrease of osmotic pressure of urine in 25mg groups until 5 weeks. The measurements of urinary pH, protein, glucose, occult blood, beta_2-microglobulin and N-acetyl-beta-D-glucosaminidase appeared no difference among three groups. Administration of GeO_2 for 13 weeks caused the enlargement of heart and kidney.