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

我们实验室已进行了关于胆道癌（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，人们注意到，死亡率较高的都道府县集中在稻米生产也很高的地区。根据这些发现，农业化学品的作用，饮食模式和其他地理特征的饮用水或土壤进行了调查。Yamamoto等分析了日本农药使用（1962-1975）与BTC（1975）标准化死亡率（SMR_s）之间的生态相关性，发现MCPA-E和MCPB-E的使用与SMR_s经常相关。虽然存在的生态相关性并不总是意味着因果关系，它可能是值得的，以揭示为什么这样的统计关联观察。作为调查生物化学的一部分， 关于我们 1）MCPA-E和MCPB-E的亚急性毒性研究用ICR雄性小鼠灌胃法评价了MCPA-E和MCPV-E的亚急性毒性。每组10只小鼠每天给予MCPA-E（50、100和200 mg/kg b.w.）和MCPB-E（25、50和100 mg/kg B.wt）每周5天，共6周。治疗结束后，观察组织学变化。除6周实验外，MCPA-E或MCPB-E连续给药12周，MCPA-E连续给药6周组小鼠的相对肝重显著增加。在6周和12周的实验中，MCPB-E和MCPPA-E各剂量组小鼠的肝脏均出现明显的组织学变化。肝肿大小鼠主要表现为肝细胞变性和中央坏死。MCPA-E和MCPB-E处理组小鼠胆囊组织学未见特异性改变。2）MCPA-E的慢性毒性研究分别喂饲2甲4氯、0（仅玉米油）、40、200、1000和5000 ppm的固体饲料1.5年，饲养1年。实验期间，当动物死亡或明显生病时，处死动物并进行组织病理学检查，与对照动物相比，在MCPA处理的动物中，经常观察到枯否细胞增加，肝细胞大小不等和晚期结节。在胆囊病理变化方面，MCPA处理的动物中乳头状增生形成明显。在给药动物中也发现了假幽门腺化生，但给药组和未给药组之间的发生率无差异。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