Carnosol is a natural compound with pharmacological action due to its anti‐cancer properties. However, the precise mechanism for its anti‐carcinogenic effect remains elusive. In this study, we used lymphoblastoid TK6 cell lines to identify the DNA damage and repair mechanisms of carnosol. Our results showed that carnosol induced DNA double‐strand breaks (DSBs). We also found that cells lacking tyrosyl‐DNA phosphodiesterase 1 (TDP1), an enzyme related to topoisomerase 1 (TOP1), and tyrosyl‐DNA phosphodiesterase 2 (TDP2), an enzyme related to topoisomerase 2 (TOP2), were supersensitive to carnosol. Carnosol was found to induce the formation of the TOP1‐DNA cleavage complex (TOP1cc) and TOP2‐DNA cleavage complex (TOP2cc). When comparing the accumulation of γ‐H2AX foci and the number of chromosomal aberrations (CAs) with wild‐type (WT ) cells, the susceptivity of the TDP1 ^−/− and TDP2 ^−/− cells were associated with an increased DNA damage. Our results provided evidence of carnosol inducing DNA lesions in TK6 cells and demonstrated that the damage induced by carnosol was associated with abnormal topoisomerase activity. We conclude that TDP1 and TDP2 play important roles in the anti‐cancer effect of carnosol.

中文翻译：

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酪氨酰-DNA磷酸二酯酶在细胞对卡诺索尔诱导的DNA损伤的耐受性中的关键作用。

卡诺索尔是一种具有药理作用的天然化合物，因为它具有抗癌特性。但是，其抗癌作用的确切机制仍然难以捉摸。在这项研究中，我们使用了淋巴母细胞TK6细胞系来鉴定鼠李糖酚的DNA损伤和修复机制。我们的结果表明，香诺酚引起DNA双链断裂（DSBs）。我们还发现缺乏与拓扑异构酶1（TOP1）相关的酪氨酰DNA磷酸二酯酶1（TDP1）和与拓扑异构酶2（TOP2）相关的酪氨酰DNA磷酸二酯酶2（TDP2）的细胞对鼠尾草酚超敏 发现鼠尾草酚可诱导TOP1-DNA裂解复合物（TOP1cc）和TOP2-DNA裂解复合物（TOP2cc）的形成。在比较γ-H2AX病灶的积累和染色体畸变（CAs）的数量时在野生型（WT）细胞中，TDP1 ^-/-和TDP2 ^-/-细胞的敏感性与DNA损伤增加有关。我们的结果提供了香诺酚诱导TK6细胞DNA损伤的证据，并证明了香诺酚诱导的损伤与异常的拓扑异构酶活性有关。我们得出的结论是，TDP1和TDP2在鼠尾草酚的抗癌作用中起着重要作用。