Studies on Abnormality of Porphyrin Metabolism Induced by Lead

铅引起的卟啉代谢异常的研究

• 批准号: 01480200
• 负责人: TOMOKUNI Katsumaro
• 金额: $ 2.88万
• 依托单位: SAGA MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480200/
• 关键词: Lead Exposure; Mice; Porphyrin Metabolism; Susceptibility; Urinary delta-Aminolevulinic Acid (ALA); ALA Synthase; ALA Dehydratase; 尿中〓ーアミノレブリン酸(ALA); 尿中δーアミノレブリン酸; δーアミノレブリン酸合成酵素; δーアミノレブリン酸脱水酵素; 個体差; 感受性差; 赤血球δーアミノレブリン酸脱水酵素; 実験小動物; 体内微量元素

The increased excretion of urinary delta-aminolevulinic acid (ALA) is one of the most specific indices for evaluating the lead-induced porphyrin metabolic disorders.In the present study, we found the significant difference in urinary ALA concentration between ddY and C57BL/6 mice strains. To deduce a possible mechanism for this difference, we measured the activities of both ALA synthase (ALAS) and ALA dehydratase (ALAD) which are regulating the concentration of ALA in the body. The activity of hepatic ALAS in ddY Mice was similar to that in C57BL/6 mice. On the other hand, a significant difference in hepatic ALAD activity was found in these mice strains.From these results, we speculated that if the relative levels of ALAS and ALAD activities in the bone marrows of mice are similar to those of ALAS and ALAD activity in the liver, the significant difference in the urinary excretion of ALA between ddY mice and C57BL/6 mice may result from the activity level of ALAD rather than ALAS.When such mice was exposed to lead in drinking water (500 ppm as Pb) for 14 days, the rate of elevated excretion of urinary ALA might be expected to differ in the two groups of mice. The data, however, has demonstrated that rate of increasing excretion of urinary ALA (7.9-times control) in lead-exposed ddY mice is almost the same as (7.6-times control) in lead-exposed C57BL/6 mice.

尿δ-氨基乙酰丙酸（ALA）排泄量的增加是评价铅中毒卟啉代谢紊乱的特异性指标之一，本研究发现ddY和C57 BL/6小鼠尿ALA浓度存在显著差异。为了推断这种差异的可能机制，我们测量了调节体内ALA浓度的ALA合成酶（ALAS）和ALA转化酶（ALAD）的活性。ddY小鼠肝ALAS活性与C57 BL/6小鼠相似。另一方面，在这些小鼠品系中发现肝脏ALAD活性的显著差异。从这些结果，我们推测，如果小鼠骨髓中ALAS和ALAD活性的相对水平与肝脏中ALAS和ALAD活性的相对水平相似，ddY小鼠尿中ALA排泄量与C57 BL/C57 BL小鼠尿中ALA排泄量相比，差异有统计学意义（P <0.05）。6只小鼠可能是ALAD而不是ALAS的活性水平所致，当这些小鼠暴露于饮用水中的铅（以Pb计500 ppm）14天时，两组小鼠尿ALA的排泄率可能不同。然而，数据表明，铅暴露的ddY小鼠的尿ALA排泄增加率（对照组的7.9倍）与铅暴露的C57 BL/6小鼠的尿ALA排泄增加率（对照组的7.6倍）几乎相同。

项目成果

Tomokuni,K: "Tolerance to lead-induced porphyrin mitabolic disorders following lead pretreatment in mice" Toxicology Letters. 54. 215-220 (1990)

Tomokuni,K：“小鼠铅预处理后对铅引起的卟啉代谢紊乱的耐受性”毒理学快报。

Tomokuni, K: "Effect of lead exposure on some biological indices related to porphyrin metabolism and the activity of erythrocyte pyrimidine 5'-nucleotidase in the mice" Arch Toxicology. 63. 23-28 (1989)

Tomokuni, K：“铅暴露对小鼠体内与卟啉代谢和红细胞嘧啶 5-核苷酸酶活性相关的一些生物指标的影响”Arch Toxicology。

Tomokuni,K: "Comparison of urinary α-aminolevulinic acid excretion and erythrocyte α-aminolevulinic acid dehydratase inhibition in different strains of mice exposed to lead" Industrial Health. 28. 31-36 (1990)

Tomokuni, K：“暴露于铅的不同品系小鼠中尿液 α-氨基乙酰丙酸排泄和红细胞 α-氨基乙酰丙酸脱水酶抑制的比较”《工业健康》28. 31-36 (1990)。

Ichiba,M: "Studies on erythrocyte pyrimidine 5-nucleotidase(P5N)test and its evaluation in workers occupationally exposed to lead" International Archives of Occupational and Environmental Health. 62. 305-310 (1990)

Ichiba，M：“职业接触铅工人的红细胞嘧啶 5-核苷酸酶（P5N）测试及其评估研究”国际职业与环境健康档案。

Tomokuni,K.: "Comparison of urinary δーaminolevulinic acid excretion and erythrocyte δーaminolevulinic acid dehydratase inhibition in different strains of mice exposed to lead" Industrial Health. 28. 31-36 (1990)

Tomokuni, K.：“暴露于铅的不同品系小鼠中尿 δ-氨基乙酰丙酸排泄和红细胞 δ-氨基乙酰丙酸脱水酶抑制的比较”工业健康 28. 31-36 (1990)。