PULMONARY TOXICITY OF SULFUR DIOXIDE AND SULFITE

二氧化硫和致癌碳氢化合物苯并（a）芘（BP）是 无处不在的空气污染物，也是烟草烟雾的组成部分。 环境暴露于这些物质是不可避免的， 仍然非常普遍。流行病学数据表明， 二氧化硫对人体呼吸道癌症的形成。 此外，大鼠和仓鼠的致瘤性研究表明， 当BP和硫联合使用时， 相对于用BP处理的那些动物， 一个人 二氧化硫本身并不致癌。 一种增强 BP的致癌性将增加海湾地区的形成 二醇环氧化物，假定的最终致癌衍生物， 通过这些活化形式BP增加DNA的共价修饰。 这 建议描述了硫的作用机理的调查 二氧化物衍生的氧化剂对转化 7，8-二羟基-7，8-二氢苯并芘（BP-7，8-diol）到bay区 二醇环氧化物，即，BP作为致癌物的最终活化步骤，以及 对特异性脱氧核苷加合物的形成的影响。 实验 系统将是短期器官培养中的完整仓鼠气管， BP诱导的肺癌模型系统。 二氧化硫 存在于中性pH值的含水体系中，以水合、离子化形式存在， 亚硫酸根阴离子。亚硫酸盐的自发或酶促氧化产生 过氧自由基和过酸衍生物，以及这些高活性氧化剂 可能参与了二氧化硫对BP致癌作用的影响。 将确定亚硫酸盐对BP-7，8-二醇代谢的依赖性影响， 特别注意亚硫酸盐氧化产物在 过程该项目研究了表达的可能目标 二氧化硫以机械方式引起毒性作用。 诸如暴露于 二氧化硫是不可避免的，这样的机制的理解， 有毒行动提供了唯一合理的基础，干预有毒 过程

Sulfur dioxide and the carcinogenic hydrocarbon benzo(a)pyrene (BP) are ubiquitous air pollutants and are components of tobacco smoke as well. Environmental exposure to these agents is unavoidable and social exposure remains far too prevalent. Epidemiologic data suggest an enhancing effect of sulfur dioxide on the formation of human respiratory tract cancers. Moreover, tumorigenicity studies in rats and hamsters have demonstrated an increased tumor yield and shortened latency period when BP and sulfur dioxide are administered together relative to those animals treated with BP alone. Sulfur dioxide itself is not carcinogenic. One way to enhance the carcinogenicity of BP would be to increase the formation of bay-region diolepoxides, the presumed ultimate carcinogenic derivatives, and to increase covalent modification of DNA by these activated forms of BP. This proposal describes a mechanistic investigation of the role of sulfur dioxide-derived oxidants on the conversion of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol) to bay-region diolepoxides, i.e., the final activation step for BP as a carcinogen, and on the formation of specific deoxyribonucleoside adducts. The experimental system will be the intact hamster trachea in short-term organ culture, a model system for BP-induced pulmonary carcinogenesis. Sulfur dioxide exists in aqueous systems at neutral pH as its hydrated, ionized form, the sulfite anion. Spontaneous or enzymatic oxidation of sulfite produces peroxyl radical and peracid derivatives, and these highly reactive oxidants may be involved in the effects of sulfur dioxide on BP carcinogenesis. Sulfite-dependent effects on BP-7,8-diol metabolism will be determined, with particular attention paid to the role of sulfite oxidation products in the process. This project examines a likely target for the expression of sulfur dioxide-induced toxic effects in a mechanistic way. As exposure to sulfur dioxide is unavoidable, such an understanding of the mechanism of toxic action provides the only rational basis for intervention in the toxic process.