Cytotoxic and mutagenic effects of tobacco-borne free fatty acids.
Cytotoxic and mutagenic effects of tobacco-borne free fatty acids.
复制标题
烟草中游离脂肪酸的细胞毒性和致突变作用。
DOI：
10.1016/j.freeradbiomed.2005.09.033
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
McGregor,WGlenn
中科院分区：
文献类型：
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作者：
Gao,Xueshan;Qian,Mingwei;Campian,JianLi;Clark,DeniseR;Burke,TomJ;Eaton,JohnW;McGregor,WGlenn
烟草烟雾中含有一种物质，能够将铁结合在水介质中，并将金属转移到有机溶剂和完整的哺乳动物红细胞中。这种铁结合活性是由于烟草烟雾中丰富的游离脂肪酸与亚铁形成2:1（游离脂肪酸：铁）螯合物。这些早期的观察结果表明，烟雾传播的游离脂肪酸和相关的肺内铁的脱位可能有助于慢性肺部炎症和与吸烟相关的致癌作用。我们现在报道，微摩尔浓度的铁或游离脂肪酸对培养的人肺成纤维细胞没有毒性。然而，当同样低浓度的铁和游离脂肪酸联合使用时，会产生协同毒性。此外，游离脂肪酸和铁的结合具有高度的诱变性，在次黄嘌呤/鸟嘌呤磷酸核糖基转移酶基因中诱导的选择性突变几乎与苯并[a]芘二聚环氧化物一样多。苯并[a]芘是香烟烟雾中存在的苯并[a]芘产生的一类致癌物质。游离脂肪酸和铁的结合也促进NIH 3T3细胞转化为锚定不依赖表型。我们得出结论，烟草烟雾中的游离脂肪酸可能是与吸烟有关的肺损伤和致癌的重要因素。
Tobacco smoke contains substances capable of binding iron in an aqueous medium and transferring the metal into both organic solvents and intact mammalian red cells. This iron-binding activity is due to free fatty acids which are abundant in tobacco smoke and form 2:1 (free fatty acid:iron) chelates with ferrous iron. These earlier observations suggested that smoke-borne free fatty acids and the associated delocalization of iron within the lung might contribute to both the chronic pulmonary inflammation and the carcinogenesis associated with smoking. We now report that micromolar concentrations of iron or free fatty acid are not toxic to cultured human lung fibroblasts. However, when combined, the same low concentrations of iron and free fatty acid exert synergistic toxicity. Furthermore, the combination of free fatty acid and iron is highly mutagenic, inducing almost as many selectable mutations in the gene for hypoxanthine/guanine phosphoribosyl transferase as does benzo[a]pyrenediolepoxide, a class I carcinogen generated from benzo[a]pyrene present in cigarette smoke. The combination of free fatty acid and iron also promotes transformation of NIH 3T3 cells into an anchorage-independent phenotype. We conclude that free fatty acids in tobacco smoke may be important contributors to both the pulmonary damage and the carcinogenesis associated with smoking.