Studies on the evaluation of health effects caused by toxic substances containing lead

含铅有毒物质对健康影响的评价研究

• 批准号: 09470102
• 负责人: TOMOKUNI Katsumaro
• 金额: $ 3.46万
• 依托单位: Saga Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470102/
• 关键词: exposure to lead; exposure to polycyclic aromatic hydrocarbons; individual difference; polymorphism of ALAD; polymorphism of CYP1A1; polymorphism of GST; DNA adducts lymphocytes; molecular epidemiology; 個人差; 発がんのリスク評価; 喫煙; 多環芳香族炭化水素(PAH); 薬物代謝

We investigated to evaluate the individual differences of health effects caused by hazardous substances such as lead and carcinogenic polycyclic aromatic hydrocarbons (PAHs). First, we studied the relationship between polymorphism of delta-aminolevulinic acid dehydratase (ALAD) and lead-induced porphyrin metabolic disorders in about 200 workers occupationally exposed to lead. Urinary concentration of delta-aminolevulinic acid (ALA) and erythrocyte ALAD inhibition were used as biological parameters of health effect by lead. However, we could not find a significant relation between polymorphism of ALAD enzyme and urinary concentration of ALA in the lead-exposed workers.Secondly, we investigated the relationship between genetic polymorphism of metabolic enzymes such as cytochrome P450 (CYP1A1) and glutathione s-transferase (GSTM1)and DNA adducts levels in lymphocytes of 51 cigarette smokers and 65 coke oven workers who are exposed to carcinogen PAHs. The measurement of DNA adducts is considered a useful indicator for environmental carcinogen exposure monitoring in humans. The data obtained demonstrated that the level of DNA adducts in lymphocytes can be influenced by not only level of exposure to PAHs but also genetic polymorphism of CYP1A1, indicating that DNA adducts levels were higher in Val/Val type of CYP1A1 than in I1/I1 and II/Val types of CYP1A1.

我们进行了调查，以评估铅和致癌多环芳烃（PAH）等有害物质对健康影响的个体差异。首先，我们研究了大约 200 名职业接触铅的工人的 δ-氨基乙酰丙酸脱水酶 (ALAD) 多态性与铅引起的卟啉代谢紊乱之间的关系。尿中 δ-氨基乙酰丙酸 (ALA) 浓度和红细胞 ALAD 抑制被用作铅对健康影响的生物学参数。然而，我们并未发现铅作业工人的ALAD酶多态性与尿ALA浓度之间存在显着关系。 其次，我们研究了细胞色素P450（CYP1A1）和谷胱甘肽S-转移酶（GSTM1）等代谢酶的遗传多态性与铅暴露工人淋巴细胞中DNA加合物水平的关系。 51名吸烟者和65名焦炉工人接触致癌物多环芳烃。 DNA 加合物的测量被认为是监测人类环境致癌物暴露的有用指标。获得的数据表明，淋巴细胞中DNA加合物的水平不仅受到PAHs暴露水平的影响，而且还受到CYP1A1基因多态性的影响，表明CYP1A1的Val/Val型的​​DNA加合物水平高于CYP1A1的I1/I1和II/Val型。

项目成果

Kiyohara C: "Relationship between aromatic DNA adduct levels and inducibility of the drug metabolizing enzymes"Med Sci Res. 27. 651-655 (1999)

Kiyohara C：“芳香族DNA加合物水平与药物代谢酶诱导性之间的关系”Med Sci Res。

Yan Y: "Different responses other than the formation of DNA adducts between the livers of carcinogen-resistant rat and carcinogen-sensitive rats to 3'-methyl-4-dimethyl-Aminoazobenzene administration"Jpn J Cancer Res. 89. 806-813 (1998)

Yan Y：“致癌物抗性大鼠和致癌物敏感大鼠的肝脏对 3-甲基-4-二甲基-氨基偶氮苯给药除了形成 DNA 加合物之外的不同反应”Jpn J Cancer Res。

Ying Yan: "different responses other than the formation of DNA adducts between the livers of carcinogen-resistant..." Japanese Journal of Cancer Research. 89. 806-813 (1998)

Ying Yan：“除了抗癌剂肝脏之间形成DNA加合物之外，还有不同的反应……”日本癌症研究杂志。

市場正良: "環境発がんのブラックボックスをさぐる"(財)労働科学研究所出版部. 195 (1999)

市场正义：《探索环境致癌的黑匣子》劳动科学研究所出版部195（1999）。

Masayoshi Ichiba: "Effect of genetic polymorphism for metabolic enzymes on the relationship between smoking dose and DNA...." Biomarkers. 3. 425-432 (1998)

Masayoshi Ichiba：“代谢酶遗传多态性对吸烟剂量和 DNA 之间关系的影响......”生物标记。