フェノキシ系除草剤の発癌性に関する遺伝毒性学的研究

苯氧基除草剂致癌性的基因毒理学研究

• 批准号: 62570227
• 负责人: YAMAMOTO Masaharu
• 金额: $ 0.9万
• 依托单位: Niigata University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570227/
• 关键词: phenoxy herbicides; MCPA-E; MCPB-E; MCPA; subacute toxicity; chronic toxicity

Epidemiological studies on the biliary tract cancer(btc) have been undertaken in our laqboratory. One reason for that is the death rate for btc in niigata prefecture is the highest in japan. In addition,it is noted that the prefectures with higher death rates clustered in the areas where the rice production was also high. Based on these findings, the role of agricultural chemicals,the dietary pattern and other geographical characteristics in drinking water or soil were investigated. First of all,the role of agricultural chemicals was tested.Yamamoto ET AL. analysed an ecological correlation between the use of chemicals (1962-1975) and standardized mortality ratios(SMR_s for BTC(1975) in japan and found that the use of MCPA-E and MCPB-E was frequently correlated with SMR_s. Although the presence of ecological correlation does not always mean the causal one, it may be worthwhile to reveal why such kind of statistical association was observed. As a part of investigation into the biochemic … More al characteristics of these compounds, subacute and chronic toxicity is examined in mice.1)Subacute toxicity study of MCPA-E and MCPB-EPhenoxy herbicides,MCPA-E and MCPV-E were evaluated for subacute toxicity by gavage in ICR male mice. Groups of 10 mice were given daily doses of MCPA-E(50, 100 and 200 mg/kg b.wt.) and MCPB-E(25, 50 and 100 mg/kg b.wt) 5 days per week for 6 weeks. After the completion of the teratment,histological changes were examined. In addition to the 6-week experiment,MCPA-E or MCPB-E was given for 12 weeks.The relative liver weight of mice in the group treated with mcpa-e for 6 weeks increased significantly. The remarkable histological change was seen in the liver of mice at all dose levels of mcpa-e and MCPB-E in the 6-and 12-wk experiments. Hepatic cell atypia and central necrosis were the major findings in mice with hepatomegaly. As to the histology of the gallbladder, the specific change was not observed in the mice treated with MCPA-E and MCPB-E.2)Chronic toxicity study of MCPAThe animals used were ICR male nice, aged 4-5 weeks old. They were given solid feed mixed with MCPA, 0(only corn oil), 40,200,1000 and 5000 ppm, for 1.5 years and bred without the treatment for 1 year. The animals were sacrificed and examined histopathologically,whenecer they were dead or visibly ill during the experiment.Im MCPA treated animals,the increase of kupffer cells, anisocytosis of hepatocytes and late nodules were frequently observed in comparison of the control animals. As to the pathological changes of the gallbladder, the proliferation of papillary formation was evident in the MCPA-treated animals. The pseudopyloric gland metaplasia was also found in the treated animals, but there was no difference in its occurrence between the treated and the untreated groups. Less

本实验室开展了胆道癌（btc）的流行病学研究。其中一个原因是新泻县的btc死亡率是日本最高的。此外，报告指出，死亡率较高的县集中在水稻产量较高的地区。在此基础上，研究了农药、膳食结构和其他地理特征在饮用水或土壤中的作用。首先，对农药的作用进行了测试。Yamamoto等人分析了化学品使用（1962-1975）与日本BTC标准化死亡率（SMR_s）之间的生态相关性，发现MCPA-E和MCPB-E的使用经常与SMR_s相关。虽然生态相关性的存在并不总是意味着因果关系，但揭示为什么会观察到这种统计关联可能是值得的。作为研究这些化合物的生化特性的一部分，我们在小鼠身上研究了亚急性和慢性毒性。1) MCPA-E和MCPB-EPhenoxy除草剂的亚急性毒性研究，通过灌胃法评价MCPA-E和MCPV-E对ICR雄性小鼠的亚急性毒性。每组10只小鼠给予每日剂量的MCPA-E（50、100和200 mg/kg b.wt.）和MCPB-E(25、50和100 mg/kg b.wt.)，每周5天，连续6周。治疗结束后观察组织学变化。在6周的实验基础上，连续12周给予MCPA-E或MCPB-E。mcpa-e治疗6周后，小鼠肝脏相对重量明显增加。在6周和12周的实验中，所有剂量的mcpa-e和MCPB-E均可使小鼠肝脏发生显著的组织学变化。肝细胞异型性和中枢坏死是肝肿大小鼠的主要表现。MCPA-E和MCPB-E处理小鼠胆囊组织学未见特异性改变。2) mcpa的慢性毒性研究。实验动物为4-5周龄的ICR雄性nice。分别饲喂MCPA、0（仅玉米油）、40,200、1000和5000ppm混合固体饲料1.5年，不加处理1年。在实验过程中，当动物死亡或明显患病时，将其处死并进行组织病理学检查。在MCPA处理的动物中，与对照动物相比，经常观察到kupffer细胞增加，肝细胞各细胞增多和晚期结节。在胆囊的病理变化方面，mcpa处理的动物胆囊乳头状增生明显。治疗组也发现假幽门腺化生，但在治疗组和未治疗组之间的发生率没有差异。少

项目成果

山本正治 他: 東北ジャーナル. 155. 385-386 (1988)

Masaharu Yamamoto 等人：东北杂志 155. 385-386 (1988)

TAKAGI,SHUKO et al.: "Subacute toxicity of MCPA and MCPB ester in mice." Jpn. J. Hyg.43. 204 (1988)

TAKAGI,SHUKO 等人：“MCPA 和 MCPB 酯对小鼠的亚急性毒性。”

高木修子: 日本衛生学雑誌. 43. 204 (1988)

高木秀子：日本卫生杂志 43. 204 (1988)

YAMAMOTO,MASAHARU et al.: "Activity of agricultural chemicals to modify mitomycin C induced growth inhibition of bacillus subtilis in the rec assay." Tohoku J. exp. Med.155. 385-386 (1988)

YAMAMOTO、MASAHARU 等人：“农用化学品修饰丝裂霉素 C 的活性，在 rec 测定中诱导枯草芽孢杆菌生长抑制。”