Penn A
Department of Environmental Medicine, New York University Medical Center, NY 10016.
Environ Health Perspect. 1989 May;81:189-92. doi: 10.1289/ehp.8981189.
Cardiovascular disease (CVD) is the single greatest cause of death in the United States and in Western Europe. There is strong epidemiologic evidence for an interaction of environmental and genetic factors in the development of clinically significant episodes of CVD. However, the specific contributions of each of these components to the onset and development of CVD remain unclear. According to the monoclonal hypothesis, arteriosclerotic plaques, the principal lesions associated with CVD, are monoclonal in origin and can be considered benign smooth muscle cells tumors of the artery wall. It follows that somatic cell alterations, possibly brought about by chemical mutagens or viruses, may play critical roles in plaque formation. During the past decade, evidence has been presented from a number of laboratories, including ours, that in animal model systems, both viruses and chemical carcinogens can play a role in the appearance and development of arteriosclerotic plaques. We have recently provided evidence consistent with the view that somatic cell alterations are critical to plaque development in man: DNA from human arteriosclerotic plaques. transforms cells in vitro and injection of these transformed cells into nude mice results in tumor formation. Thus, plaque DNA behaves similarly to tumor DNA under defined assay conditions.
心血管疾病（CVD）是美国和西欧单一最大的死因。有强有力的流行病学证据表明，环境因素与遗传因素在临床上显著的心血管疾病发作过程中相互作用。然而，这些因素各自对心血管疾病的发病和发展的具体作用仍不清楚。根据单克隆假说，动脉粥样硬化斑块是与心血管疾病相关的主要病变，其起源是单克隆的，可被视为动脉壁的良性平滑肌细胞瘤。由此可见，可能由化学诱变剂或病毒引起的体细胞改变，可能在斑块形成中起关键作用。在过去十年中，包括我们实验室在内的许多实验室都已提出证据表明，在动物模型系统中，病毒和化学致癌物都可在动脉粥样硬化斑块的出现和发展中起作用。我们最近提供的证据与体细胞改变对人类斑块发展至关重要这一观点一致：来自人类动脉粥样硬化斑块的DNA在体外可转化细胞，将这些转化细胞注射到裸鼠体内会导致肿瘤形成。因此，在特定的检测条件下，斑块DNA的行为与肿瘤DNA相似。
