Thebaine is an alkaloid and can be found in poppy seeds in relatively high concentrations. Acute toxicity of thebaine is fairly high, but not much is known about chronic toxicity. To investigate the genotoxicity of thebaine, cytokinesis-block micronucleus test and comet assay were conducted in TK6 cells. In addition, effects of putative thebaine metabolites were analysed using metabolically active HepG2 cells and TK6 cells with S9 mix. FDA test and trypan blue test were used together with the frequency of mitotic and apoptotic cells to assess potential cytotoxicity of thebaine treatment. Micronucleus induction was observed after high doses (150 and 500 μM) of thebaine without metabolic activation in the presence of slight to moderate cytotoxicity. No effects were observed in the comet assay or after metabolic activation up to the highest dose of 500 μM. A potential protective effect on micronucleus induction after thebaine treatment was investigated via co-treatment with MMC and BaP in TK6 cells. Only after co-treatment with MMC, a reduction of micronucleus frequency was found. Overall, this study shows a potential of thebaine to induce genotoxic effects at high concentrations. The observation of cytotoxicity at these concentrations supports the hypothesis that genotoxicity may be caused by cytotoxic effects. Further studies will need to elucidate whether these effects are directly genotoxic or indeed result from cytotoxicity.

蒂巴因是一种生物碱，可以在罂粟种子中以相对较高的浓度找到。蒂巴因的急性毒性相当高，但对慢性毒性知之甚少。为了研究蒂巴因的遗传毒性，在TK6细胞中进行了胞质分裂阻断微核试验和彗星试验。此外，使用代谢活跃的 HepG2 细胞和 TK6 细胞与 S9 混合物分析推定蒂巴因代谢物的影响。FDA 测试和台盼蓝测试与有丝分裂和凋亡细胞的频率一起用于评估蒂巴因治疗的潜在细胞毒性。在存在轻度至中度细胞毒性的情况下，在没有代谢激活的情况下，在高剂量（150 和 500 μM）蒂巴因后观察到微核诱导。在彗星试验中或在最高剂量 500 μM 的代谢激活后未观察到任何影响。通过与 TK6 细胞中的 MMC 和 BaP 共同处理，研究了蒂巴因处理后对微核诱导的潜在保护作用。只有在与 MMC 共同处理后，才发现微核频率降低。总体而言，这项研究显示了蒂巴因在高浓度下诱导基因毒性作用的潜力。在这些浓度下观察到的细胞毒性支持基因毒性可能由细胞毒性作用引起的假设。进一步的研究需要阐明这些影响是直接遗传毒性还是确实由细胞毒性引起。只有在与 MMC 共同处理后，才发现微核频率降低。总体而言，这项研究显示了蒂巴因在高浓度下诱导基因毒性作用的潜力。在这些浓度下观察到的细胞毒性支持基因毒性可能由细胞毒性作用引起的假设。进一步的研究需要阐明这些影响是直接遗传毒性还是确实由细胞毒性引起。只有在与 MMC 共同处理后，才发现微核频率降低。总体而言，这项研究显示了蒂巴因在高浓度下诱导基因毒性作用的潜力。在这些浓度下观察到的细胞毒性支持基因毒性可能由细胞毒性作用引起的假设。进一步的研究需要阐明这些影响是直接遗传毒性还是确实由细胞毒性引起。