Coexposure to benzo[a]pyrene and UVA induces DNA damage: First proof of double‐strand breaks in a cell‐free system
Coexposure to benzo[a]pyrene and UVA induces DNA damage: First proof of double‐strand breaks in a cell‐free system
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DOI：
10.1002/em.20166
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发表时间：
2006-01
影响因子：
2.8
通讯作者：
T. Toyooka;Y. Ibuki;Fumiyo Takabayashi;R. Goto
中科院分区：
文献类型：
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作者：
T. Toyooka;Y. Ibuki;Fumiyo Takabayashi;R. Goto
紫外线辐射引起的DNA损伤在皮肤癌的发生中起重要作用。虽然UVA构成了太阳紫外线辐射的大部分，但它对DNA的伤害比UVB小。然而，在光敏剂存在下，UVA辐射产生的DNA损伤可以增强。我们以前使用苯并[a]芘（BaP），一种环境致癌的多环芳烃，作为外源性光敏剂，并证明联合暴露于BaP和UVA导致培养的中国仓鼠卵巢（CHO-K1）细胞中DNA双链断裂（DSB）。在这项研究中，我们研究了BaP和UVA共同暴露是否会在无细胞系统中诱导DSB，以及活性氧（ROS）是否参与DSB的产生。在无细胞系统（体外）和CHO-K1细胞（体内）中，通过共暴露诱导DSB，但单独使用BaP或UVA处理则不会诱导DSB。DSB诱导在体外需要更高剂量的UVA和BaP比在体内所需的，这表明DSB诱导的机制不同。在体外和体内共暴露于BaP和UVA时，在8-oxo-7，8-dihydro-2′-deoxyguanosine（8-oxodG）的形成中也观察到类似的效率差异。单线态氧（1 O2）清除剂（NaN 3）可有效抑制DSB和8-oxodG的产生，表明1 O2是BaP和UVA在体外和体内产生的主要ROS。此外，修复缺陷xrs-5细胞对BaP和UVA的共同暴露比CHO-K1细胞更敏感，但这两种细胞系对NaN 3存在下的联合处理同样敏感。这一结果表明，由BaP和UVA共暴露产生的细胞死亡至少部分是由于1 O2产生的DSB。我们的研究结果表明，BaP和UVA的共同暴露有效地诱导DNA损伤，特别是DSB，这导致光毒性和可能的光致癌作用。Environ.摩尔诱变剂，2006.© 2005 Wiley利斯公司
DNA damage induced by solar ultraviolet (UV) radiation plays an important role in the induction of skin cancer. Although UVA constitutes the majority of solar UV radiation, it is less damaging to DNA than UVB. The DNA damage produced by UVA radiation, however, can be augmented in the presence of a photosensitizer. We previously used benzo[a]pyrene (BaP), an environmental carcinogenic polycyclic aromatic hydrocarbon, as an exogenous photosensitizer, and demonstrated that combined exposure to BaP and UVA resulted in DNA double‐strand breaks (DSBs) in cultured Chinese hamster ovary (CHO‐K1) cells. In this study, we investigated whether coexposure to BaP and UVA induces DSBs in a cell‐free system and whether reactive oxygen species (ROS) were involved in the generation of the DSBs. DSBs were induced by the coexposure both in the cell‐free system (in vitro) and in CHO‐K1 cells (in vivo), but not by treatment with BaP or UVA alone. DSB induction in vitro required higher doses of UVA and BaP than were required in vivo, suggesting that the mechanism of DSB induction differed. A similar difference in efficiency also was observed in the formation of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) by coexposure to BaP and UVA in vitro and in vivo. A singlet oxygen (1O2) scavenger (NaN3) effectively inhibited the production of DSBs and 8‐oxodG, suggesting that 1O2 is a principal ROS generated by BaP and UVA both in vitro and in vivo. Furthermore, repair‐deficient xrs‐5 cells were more sensitive to coexposure with BaP and UVA than were CHO‐K1 cells, but the two cell lines were equally sensitive to the combined treatment in the presence of NaN3. This result suggested that the cell death produced by coexposure to BaP and UVA was at least partly due to the DSBs generated by 1O2. Our findings indicate that coexposure to BaP and UVA effectively induced DNA damage, especially DSBs, which results in phototoxicity and possibly photocarcinogenesis. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.