摘要
本项研究是以雪貂（Ｆｅｒｒｅｔ）和旱獭（Ｗｏｏｄｃｈｕｃｋ）作为实验动物模型，由于这两种动物的某些器官特征在解剖学上和生理学上与人类有其相似之处，试图通过雪貂和旱獭体内生物合成亚硝胺，说明人类暴露于化学致场物亚硝胺的另外一个来源是生物体内合成。同时，用烷基化学致癌物二甲基亚硝胺对旱獭进行ＤＮＡ烷基化的研究，发现由于被旱獭肝炎病毒（ＷＨＶ，ＷｏｏｄｃｈｕｃｋＨｅｐａｔｉｔｉｓＶｉｒｕｓ）感染的旱獭，不仅体内易于合成亚硝胺，而且其肝脏组织ＤＮＡ烷基化的水平高于对照组。以ＤＮＡ烷基化反应产生的烷化核酸碱基作为生物标志（Ｒｉｏｍａｒｋｅｒｓ），对于胃癌高发区人群尿中的烷化核酸碱基进行定量测定，并与低发区相对照，显示两者之间有差异性。本项研究为从动物实验外推到人群的设想提供了启示，还提出了以生物标志作为建立分子流行病学的依据。
This project has begun to evalute the ferret and woodchuck as the experimental modelsfor etiology study of stomach cancer , because the organic characters of the two animals areanatomically and physiologically similar to the human. We want to do working about the en-dogenous biosyntheis for nitrosamine in the ferret and woodchuck ,then it is to explain thatthe human expose to the carcinogens nitrosamines which from the anather resources of theendogenous biosynthesis, in the meantime, fistly, the woodchuck was infected with thewoodchuck hepatitis virus(WHV) , then we have studied about the DNA alkylation in thewoodchuck with the alkylating cacinogen dimethylnitrosamine, we not only found that theendogenors biosynthesis for nitrosamine easy, but also the-alkylation of the liver DNA ishigher than the control group. We take the alkylated nucleic acid bases as the biomakers forthe DNA alkylation, however, the results are different between the population at the highrisk for stomach cancer and the population at the control group. This project shown that itaraws inspiration from the animal experiment then it could be extrapolated to the human,and it also furnished the evidence for founding molecular epidemiology by the biomarkers.
基金
国家自然科学基金
关键词
雪貂
旱獭
医学实验
实验模型
胃肿瘤
病因
endogenous biosynthesis of nitrosamine : DNA alkylation
biomarkers
molecularepidemiology.
