Department of Health Risk Analysis and Toxicology, Research Institute School of Nutrition, Metabolism and Toxicology, Maastricht University, PO box 616, 6200 MD Maastricht, The Netherlands.
Carcinogenesis. 2009 Dec;30(12):2070-6. doi: 10.1093/carcin/bgp186.
Beta-carotene (BC) was found to enhance lung cancer risk in smokers. This adverse effect was unexpected because BC was thought to act as an anti-oxidant against cigarette smoke-derived radicals. These radicals can directly or indirectly damage DNA, leading to the formation of pro-mutagenic DNA lesions such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 3-(2-deoxy-beta-D-erythro-pentafuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one deoxyguanosine (M(1)dG). Later, it was suggested that high concentrations of BC could also result in pro-oxidant effects. Therefore, we investigated whether high but physiologically feasible concentrations of BC were able to alter (i) the formation of radicals in vitro assessed by electron spin resonance spectroscopy, (ii) the levels of 8-oxo-dG and M(1)dG in vitro in lung epithelial cells after incubation with hydrogen peroxide (H(2)O(2)) and the smoke-derived carcinogen benzo[a]pyrene (B[a]P) and (iii) the levels of 8-oxo-dG and M(1)dG in vivo in ferrets' lung after chronic exposure to B[a]P. BC increased in vitro hydroxyl radical formation in the Fenton reaction but inhibited the formation of carbon-centered radicals. Similarly, BC was able to enhance 8-oxo-dG in vitro in lung epithelial cells. On the other hand, BC significantly inhibited M(1)dG formation in lung epithelial cells, especially after induction of M(1)dG by H(2)O(2) or B[a]P. Finally, BC supplementation of ferrets also resulted in a significant decrease in M(1)dG, but in contrast to the in vitro experiments, no effect was observed on 8-oxo-dG levels, probably because of increased base excision repair capacities as assessed by a modified comet assay. These data indicate that the fate of BC being a pro- or anti-oxidant strongly depends on the type of radical involved.
β-胡萝卜素 (BC) 被发现会增加吸烟者患肺癌的风险。这种不利影响出乎意料，因为 BC 被认为可以作为一种抗氧化剂来对抗香烟烟雾中产生的自由基。这些自由基可以直接或间接地损伤 DNA，导致形成促突变的 DNA 损伤，如 8-氧-7,8-二氢-2'-脱氧鸟苷 (8-氧-dG) 和 3-(2-脱氧-β-D-赤式-戊呋喃糖基)嘧啶并[1,2-α]嘌呤-10(3H)-酮脱氧鸟苷 (M(1)dG)。后来，人们认为高浓度的 BC 也可能产生促氧化剂作用。因此，我们研究了高但生理上可行的 BC 浓度是否能够改变：（i）通过电子自旋共振光谱评估的体外自由基形成；（ii）用过氧化氢 (H(2)O(2)) 和香烟衍生的致癌剂苯并[a]芘 (B[a]P) 孵育肺上皮细胞后体外 8-氧-dG 和 M(1)dG 的水平；（iii）慢性暴露于 B[a]P 后，体内雪貂肺中的 8-氧-dG 和 M(1)dG 水平。BC 增加了 Fenton 反应中的羟基自由基形成，但抑制了碳中心自由基的形成。类似地，BC 能够增强肺上皮细胞中的 8-氧-dG。另一方面，BC 显著抑制了肺上皮细胞中 M(1)dG 的形成，尤其是在 H(2)O(2)或 B[a]P 诱导 M(1)dG 形成后。最后，BC 补充剂也导致雪貂的 M(1)dG 显著减少，但与体外实验相反，8-氧-dG 水平没有受到影响，可能是由于碱基切除修复能力增加，如通过改良彗星试验评估的那样。这些数据表明，BC 作为氧化剂还是抗氧化剂的命运强烈取决于所涉及的自由基类型。
