O3 AND MODULATING CR TOXICITY AND THE LUNG

大多数与职业有关的化学品危害的研究都涉及使用 单一污染物，因此生物和安全影响， 在评价中，通常忽略了实际混合物的吸入 与工人的健康和安全有关。在这方面，铬（Cr）是 在焊接过程中与臭氧（O3）一起释放， 吸入暴露于含铬材料是肺癌;这是 这可能主要是由于烟气中的不溶性Cr物质。但 其他共吸入物在调节铬引发的反应中的作用 还不清楚。共污染物可能会改变肺部环境 生产条件，可以提高铬的形成和生存， 引发肿瘤。例如，已经证明， 错误吸入的O3会增加吸入的 不溶性铬颗粒;这可能是一个场景的一部分， 最终导致肺内的条件传导到 铬引发的瘤形成和存活。这项建议 研究肺癌发病率升高的其他机制 暴露于含有Cr和O3的焊接烟雾的焊工的发病率。它 假设不溶性Cr（VI）在 吸入Cr/O_3混合气体的宿主的肺比宿主的肺大 由于肺组织中O3介导的增加，仅吸入Cr Cr（VI）的负担和/或一种或多种记录的 遗传/表观遗传机制与铬诱导的转换， 正常细胞转化为转化类型（即，DNA水平的提高 损伤、染色体畸变和/或诱导活性增加 已知调节新生癌基因表达的细胞激酶） 由于O3的作用， 不溶性Cf（VI）颗粒的细胞内。该项目涉及暴露 大鼠的大气中含有致癌的铬（VI），即钙 铬酸盐，单独和与O3组合。这项研究将提高我们的 理解铬和铬之间相互作用的机制， 肺中的O3和空气污染物混合物可能发挥的作用 在肺部疾病发病机制后，暴露于现实的混合 与职业相关的氛围。

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.