Baker D L, Krol E S, Jacobsen N, Liebler D C
Department of Pharmacology and Toxicology, College of Pharmacy, and Department of Chemistry, University of Arizona, Tucson, Arizona 85721-0207, USA.
Chem Res Toxicol. 1999 Jun;12(6):535-43. doi: 10.1021/tx980263v.
Recent intervention trials reported that smokers given dietary beta-carotene supplementation exhibited an increased risk of lung cancer and overall mortality. beta-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. We have examined the interactions of cigarette smoke with beta-carotene in model systems. Both whole smoke and gas-phase smoke oxidized beta-carotene in toluene to several products, including carbonyl-containing polyene chain cleavage products and beta-carotene epoxides. A major product of the reaction was identified as 4-nitro-beta-carotene, which was formed by nitrogen oxides in smoke. Both cis and all-trans isomers of 4-nitro-beta-carotene were detected. The hypothesis that smoke-driven beta-carotene autoxidation exerts prooxidant effects was tested in a liposome system. Lipid peroxidation in dilinoleoylphosphatidylcholine liposomes exposed to gas-phase smoke was modestly inhibited by the incorporation of 0.1 mol % beta-carotene. Both the lipid soluble antioxidant alpha-tocopherol and the water soluble antioxidant ascorbate were oxidized more slowly by gas-phase smoke exposure in liposomes containing beta-carotene. These data indicate that beta-carotene exerts weak antioxidant effects against smoke-induced oxidative damage in vitro. It is unlikely that a prooxidant effect of beta-carotene occurs under biologically relevant conditions or is responsible for an increased incidence of lung cancer observed in smokers who consume beta-carotene supplements.
近期的干预试验报告称，补充膳食β-胡萝卜素的吸烟者患肺癌和总体死亡率的风险增加。据推测，β-胡萝卜素在暴露于烟雾的肺部充当促氧化剂，从而促进肺癌发生。我们在模型系统中研究了香烟烟雾与β-胡萝卜素的相互作用。全烟雾和气相烟雾均将甲苯中的β-胡萝卜素氧化为多种产物，包括含羰基的多烯链裂解产物和β-胡萝卜素环氧化物。该反应的一种主要产物被鉴定为4-硝基-β-胡萝卜素，它是由烟雾中的氮氧化物形成的。检测到了4-硝基-β-胡萝卜素的顺式和全反式异构体。在脂质体系统中测试了烟雾驱动的β-胡萝卜素自氧化发挥促氧化作用的假设。在含有0.1 mol%β-胡萝卜素的情况下，暴露于气相烟雾的二亚油酰磷脂酰胆碱脂质体中的脂质过氧化受到适度抑制。在含有β-胡萝卜素的脂质体中，脂质可溶性抗氧化剂α-生育酚和水溶性抗氧化剂抗坏血酸在气相烟雾暴露下氧化得更慢。这些数据表明，β-胡萝卜素在体外对烟雾诱导的氧化损伤发挥微弱的抗氧化作用。在生物学相关条件下，β-胡萝卜素不太可能产生促氧化作用，也不太可能是食用β-胡萝卜素补充剂的吸烟者中观察到的肺癌发病率增加的原因。
