O3 AND MODULATING CR TOXICITY AND THE LUNG

O3 与调节 CR 毒性和肺部

• 批准号: 6223992
• 负责人: Richard B Schlesinger
• 金额: $ 41.18万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6223992
• 关键词: DNA damage; air pollution; chromium; chromosome aberrations; comorbidity; disease /disorder proneness /risk; environmental contamination; gene expression; laboratory rat; lung neoplasms; occupational health /safety; oncogenes; ozone; pathologic process; pollutant interaction; protein kinase

Most studies of occupationally relevant chemical hazards have involved use of single contaminants, so the biological and safety implications from inhalation of realistic mixtures have commonly been ignored in evaluations related to worker health and safety. In this regard, chromium (Cr) is released with ozone (O3) during welding, and a major health hazard from inhalation exposure to Cr-containing materials is lung cancer; this is likely due largely to the insoluble Cr species in the fumes. However, the contribution from other co-inhalants in modulating Cr-initiated responses is not clear. Co-contaminants may change the pulmonary environment producing conditions which could enhance the formation and survival of Cr- initiated tumors. For example, it has been demonstrated that simultaneously-inhaled O3 increases the pulmonary retention of inhaled insoluble Cr particles; this could be part of a scenario which would ultimately give rise to conditions within the lungs conductive to the formation and survival of Cr-initiated neoplasia. This proposal investigates other mechanisms underlying the elevated lung cancer incidence in welders exposed welding fumes containing both Cr and O3. It is hypothesized that the carcinogenic potential of insoluble Cr(VI) in the lungs of hosts inhaling the Cr/O3 mixture is greater than that in hosts inhaling the Cr alone due to O3-mediated increases in the lung tissue burdens of Cr(VI) and/or augmentation of one or more of the documented genetic/epigenetic mechanisms associated with Cr-induced conversion of normal cells to transformed types (i.e., an enhancement in level of DNA damage, chromosomal aberrations, and/or induced increases in the activity of cell kinases known to regulate the expression of nascent oncogenes) arising from the effects of O3 upon mechanisms utilized for the intracellular of insoluble Cf(VI) particles. The project involves exposure of rats to atmospheres containing carcinogenic Cr(VI), namely calcium chromate, alone and in combination with O3. This study will improve our understanding of the mechanisms underlying the interaction between Cr and O3 in the lungs and the role which mixtures of air contaminants may play in pulmonary disease pathogenesis following exposure to realistic mixed atmospheres of occupational relevance.

大多数与职业相关的化学危害的研究都涉及使用 单一污染物，因此生物和安全影响 在评估中通常会忽略吸入真实混合物 关系到工人的健康和安全。在这方面，铬（Cr）是 焊接过程中释放出臭氧（O3），对健康造成重大危害 吸入接触含铬物质会导致肺癌；这是 可能主要是由于烟雾中存在不溶性铬物质。然而， 其他共同吸入剂在调节 Cr 引发的反应中的贡献 尚不清楚。共污染物可能会改变肺部环境 可以增强Cr-的形成和存活的生产条件 引发肿瘤。例如，已经证明 同时吸入 O3 会增加吸入氧气的肺潴留 不溶性Cr颗粒；这可能是场景的一部分 最终引起肺部内的状况，从而导致 Cr 引发的肿瘤的形成和存活。这个提议 研究肺癌升高的其他机制 暴露在含有 Cr 和 O3 的焊接烟雾中的焊工的发病率。它 据推测，不溶性 Cr(VI) 的致癌潜力 吸入Cr/O3混合物的宿主的肺部比宿主体内的肺部更大 由于 O3 介导的肺组织增加而单独吸入 Cr Cr(VI) 的负担和/或一种或多种已记录的物质的增加 与 Cr 诱导的转化相关的遗传/表观遗传机制 正常细胞转化为转化类型（即 DNA 水平增强） 损伤、染色体畸变和/或诱导的活性增加 已知调节新生癌基因表达的细胞激酶） 源于 O3 对所用机制的影响 细胞内不溶性 Cf(VI) 颗粒。该项目涉及曝光 大鼠接触含有致癌物质 Cr(VI)（即钙）的大气 铬酸盐，单独使用或与 O3 结合使用。这项研究将改善我们 了解 Cr 和 Cr 之间相互作用的机制 肺部中的 O3 以及空气污染物混合物可能发挥的作用 暴露于现实混合环境后肺部疾病的发病机制 与职业相关的氛围。