自由基介导砷的有害影响

2001年2月12日纽约，2001年2月12日 - 砷的癌症造成的金属，通过促进哥伦比亚研究人员报告，通过提高身体的破坏性化学品的损坏化学品来施加有害影响。新研究发表于2月13日美国国家科学院的讨论，增加了越来越多的证据，即促进自由基的抗氧化剂的营养物质可能有助于预防因砷，镉而引起的癌症和其他疾病。和石棉。抗氧化剂的来源包括人类饮食中常见的维生素和微量营养素，如维生素C，维生素E和硒。“砷是EPA超级邮财名单上的最高环境污染物之一，”该研究的主要作者汤姆K. Hei博士说。“这项研究提供了第一种明确的证据，即环境致癌主要通过自由基途径。”赫西博士是哥伦比亚大学医师和外科医生放射性研究中心放射肿瘤学教授。“如果我们了解砷是如何导致癌症的，我们将有更好的预防方法。”他说，抗氧化剂是这种预防措施的主要候选人。该研究还涉及P＆S皮肤科研究人员和研究人员Albert Einstein医学和科罗拉多州立大学，表明，在实验室中培养的细胞在暴露于砷化合物的五分钟内大大增加了自由基生产。该化合物，砷酸钠 - 环境中砷的主要毒性形式 - 还提高了细胞中突变的速率。 Mutations are a key step in cancer development. The mutation rate shot up still higher when researchers added a chemical that reduced the cells' production of natural antioxidants. This was consistent with previous research suggesting that antioxidants can protect cells from arsenic-induced genetic damage. Close to a million U.S. residents are exposed to unsafe levels of arsenic, especially in the Southwest, says Dr. Hei. And the problem is substantially worse in some other countries. One study showed arsenic contaminates 27 percent of drinking wells in certain parts of Bangladesh and India, at levels more than 10 to 20 times higher than the maximum level the EPA has deemed safe. Arsenic, a natural component of the Earth's crust, can enter the body primarily in two ways. One is through ingestion, such as through contaminated water, food, or drugs. Another is by inhalation, usually resulting from workplace exposure in industries such as ore smelting, semiconductor and glass manufacturing, and the burning of arsenic-tainted coal. Diseases associated with chronic arsenic exposure include lung, skin, bladder, and liver cancers, diabetes, atherosclerosis, kidney failure, liver and nervous system damage, and keratosis, a skin disease. "In addition to the gene and chromosomal mutations that we have illustrated in this study, the oxidative damage is likely to contribute to other arsenic-associated human diseases as well. This includes cardiovascular and renal abnormalities," says Dr. Hei. How arsenic induces human cancer has been somewhat of a mystery for two reasons. First, arsenic is an oddball among human carcinogens in that it has not been shown to cause cancer in laboratory animals. Second, laboratory research on the mutagenic effect of arsenic in mammalian cells has turned up nothing. This has puzzled scientists because epidemiological studies have established that arsenic is a human carcinogen, and mutations are generally a crucial first step in the development of cancer. Dr. Hei and colleagues believe rodents such as those used for research have cellular mechanisms that protect them from arsenic damage. They also speculate that the types of mutations induced by arsenic are large chromosomal losses that are hard to detect with conventional mutation assays. When arsenic deletes the monitored gene, it also might delete crucial genes nearby, thus killing the cells. To circumvent these problems, Dr. Hei and colleagues used a line of hybrid human-animal cells. These are hamster ovary cells containing a copy of human chromosome No. 11 in addition to their own chromosomes. Since these cells can live despite damage to the human chromosome, the number of mutants can be measured by the absence or presence of surface antigens that are coded by the human chromosome. Using these and other techniques, Dr. Hei and colleagues developed data suggesting arsenic acts through a series of chemical reactions in the cell that produce free radicals. Free radicals form naturally in the body during oxygen metabolism, but their levels rise with the presence of some toxins. They are harmful because they tend to interact strongly with nearby molecules, changing the structure of cellular components such as DNA. Using a spin trapping assay, Dr. Hei's team showed that arsenic acts by first spurring production of superoxide, a very unstable free radical species that is rapidly being converted into hydrogen peroxide by enzymes in the cells. The hydrogen peroxides are in turn converted into hydroxyl radicals, extremely reactive and damaging free radicals that attack cell membranes and DNA to create mutations. "As such, antioxidants could be an interventional approach in patients who have been subjected to chronic arsenic exposure," says Dr. Hei. He plans to extend the study to determine the source of these radical species, in particular the role of mitochondria in mediating the genotoxic effects of arsenic. The research was supported by the EPA and the National Institutes of Health.

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