Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica
Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica
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DOI：
10.1080/009841096161203
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发表时间：
1996-08-09
期刊：
影响因子：
--
通讯作者：
Miller, MR
中科院分区：
文献类型：
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作者：
Miles, PR;Ma, JYC;Miller, MR
由于一些证据表明矽肺可能会增加肺癌的发病率，而且先前的研究表明，接触二氧化硅会改变大鼠肺细胞色素P-450系统，因此我们研究了接触二氧化硅对苯并[a]芘(BaP)肺微粒体代谢的影响。大鼠气管内染尘，2wk后取未染尘和染矽尘动物的肺组织，测定其微体组织和代谢产物的含量。比较两个染尘组肺微体组织中BaP代谢物的形成，3-OH BaP、BaP 4，5-二醇和BaP 9，10-二醇减少45-70%，但BaP 7，8-二醇或BaP-苯二酚的形成没有明显改变。事实上，在大鼠暴露于二氧化硅后，同等数量的肺微体组织产生的BaP饮食和BaP苯醌(潜在的有毒代谢物)与相对无毒的3-OH BaP的比例增加了三倍以上。由于大鼠暴露在二氧化硅中会导致肺微体蛋白水平增加，因此计算了肺中所有微体组织可以产生的BaP代谢物的数量。在二氧化硅处理的动物中，计算出的3-OH BaP、BaP 4，5-二醇和BaP 9，10-二醇的总肺产量往往增加1.2-2.0倍，但BaP 7，8-二醇和BaP对苯二酚增加3.5倍。这些结果表明，暴露于二氧化硅可以改变大鼠肺代谢苯并[a]芘的能力，其中最大的影响似乎是促进了BaP 7，8-二醇和BaP对苯二酚的积累。
Because some evidence suggests that there may be an increased incidence of lung cancer in silicosis and because previous studies have shown that exposure of rats to silica alters the pulmonary cytochrome P-450 system, we studied the effects of exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene (BaP). Rats were exposed to silica by intratracheal administration, lung microsomes were obtained 2 wk later from untreated and silica-treated animals, and the amounts of microsomal tissue and metabolites formed during the in vitro microsomal metabolism of BaP were measured. When the formation of BaP metabolites in equal amounts of lung microsomal tissue from the 2 treatment groups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9, 10-diol are reduced by 45-70%, but the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered following exposure to silica. In fact, the ratio of the BaP diets and BaP quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP produced by equal amounts of lung microsomal tissue is increased more than threefold following exposure of rats to silica. Since exposure of rats to silica leads to increased levels of lung microsomal protein, the amounts of BaP metabolites that could be produced by all microsomal tissue in the lungs were calculated. In silica-treated animals, the calculated total lung production of 3-OH BaP, BaP 4,5-diol, and BaP 9, 10-diol tends to be increased by 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These results demonstrate that exposure of rats to silica may alter the capacity of the lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced accumulation of BaP 7,8-diol and the BaP quinones.