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

本实验室对胆道癌进行了流行病学研究。其中一个原因是新泻县的btc死亡率是日本最高的。此外，人们注意到，死亡率较高的县集中在水稻产量也较高的地区。基于这些发现，调查了农药在饮用水或土壤中的作用、饮食结构和其他地理特征。首先，检验了农用化学品的作用。分析了日本化学品使用(1962-1975)和标准化死亡率(SMR_S，1975年)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，但为什么观察到这种统计相关性是值得观察到的。作为生物化学…研究的一部分MCPA-E和MCPB-EPhenoxy除草剂的亚急性毒性研究，MCPA-E和MCPV-E对ICR雄性小鼠的亚急性毒性试验。每天给10只小鼠灌胃MCPA-E(50、100和200 mg/kg体重)。MCPB-E(25、50和100 mg/kg体重)，每周5天，共6周。处理完成后，观察组织学变化。在6周实验的基础上，给予MCPA-E或MCPB-E治疗12周，MCPA-e治疗6周组小鼠肝脏相对重量显著增加。在6周和12周的实验中，所有剂量的MCPA-e和MCPB-E的小鼠肝脏均出现了显著的组织学变化。肝细胞异型性和中心性坏死是肝肿大小鼠的主要表现。MCPA-E组和MCPB-E组小鼠的胆囊壁组织学无明显变化。2)MCPA-E和MCPB-E组小鼠的慢性毒性试验。饲喂含MCPA、0(仅含玉米油)、40、200、1000、5000ppm的固体饲料，饲养1.5年，不加处理饲养1年。实验期间动物死亡或明显患病后，处死动物并进行组织病理学检查。在MCPA处理的动物中，与对照组相比，Kupffer细胞增多，肝细胞不等同，结节较晚。对于胆囊壁的病理改变，MCPA处理组动物可见明显的乳头状结构的增殖。用药组动物也出现假幽门腺化生，但用药组与未用药组比较差异无统计学意义。较少

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