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Study of tobacco smoke-induced DNA damage in association with carcinogenicity using multi organ mouse SCG assay.

使用多器官小鼠 SCG 测定研究烟草烟雾引起的 DNA 损伤与致癌性的关系。

基本信息

批准号：
11660308
负责人：
TSUDA Shuji
金额：
$ 2.3万
依托单位：
IWATE UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660308/
关键词：
tobacco smoke carcinogenicity DNA damage SCG method free radical 8-OH-dG food additives マウス多臓器コメット法

项目摘要

We tested the genotoxicity of cigarette smoke in the organs of the mouse using the alkaline single cell gel electrophoresis (SCG, or comet) assay. We also tested the effect of free radical scavengers on the genotoxicity of the smoke. After the animals were exposed to smoke, SSB appeared in the lung, stomach, and liver. Either VC or VE (100 mg/kg/day) pretreatment completely prevented SSB in the lung, stomach, and liver. Thus, the SCG assay detected DNA SSB induced by cigarette smoke in the known target organ, two possible target organs, and none of the non-target organs ; antioxidants could prevent those effects, suggesting that free radicals may have been a source of the damage. Our results suggest the importance of SCG assay as a tool in the studies of genotoxicity and carcinogenicity. 8-OH dG was not detected by HPLC with ECD detector after the inhalation of tobacco smoke. Then, we determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including Japan. For the preliminary assessment, we treated pregnant mice with amaranth (Food Red No.2), allura red (Food Red No.40), or acid red (Food Red No.106). The assay was positive in the colon after the administration of amaranth and allura red. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. Thus, we tested male mice with amaranth, allura red, and new coccine (Food Red No.18). The three dyes induced DNA damage in the colon starting at 10 mg/kg. Because the three azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.

我们用碱性单细胞凝胶电泳法(SCG，或彗星)检测了香烟烟雾对小鼠器官的遗传毒性。我们还测试了自由基清除剂对烟雾遗传毒性的影响。动物暴露在烟雾中后，肺、胃和肝脏出现了SSB。Vc或VE(100 mg/kg/d)可完全阻止肺、胃和肝脏的SSB。因此，SCG检测在已知的靶器官中检测到香烟烟雾诱导的DNA SSB，两个可能的靶器官，而不是非靶器官；抗氧化剂可以阻止这些影响，这表明自由基可能是损害的来源。我们的结果表明，SCG检测作为研究遗传毒性和致癌性的工具具有重要意义。吸入烟草烟雾后，用高效液相色谱-电子捕获检测器未检测到8-羟基-DG。然后，我们测定了目前在包括日本在内的许多国家用作食品着色剂的合成红焦油染料的遗传毒性。在初步评估中，我们用紫红色(食品红2号)、金露红(食品红40号)或酸性红(食品红106号)处理怀孕小鼠。在给予紫红色和紫红色后，结肠中的检测呈阳性。酸性红在任何采样时间均未引起DNA损伤。这些染料都没有破坏其他器官或胚胎的DNA。因此，我们用紫红色、紫红色和新的鸡肉(食用红18号)来测试雄性小鼠。这三种染料从10 mg/kg开始就会引起结肠的DNA损伤。由于我们研究的三种偶氮添加剂在非常低的剂量下会导致结肠DNA损伤，因此有必要对偶氮添加剂进行更广泛的评估。