Thallium (Tl) and its two cationic species, Tl(I) and Tl(III), are toxic for most living beings. In this work, we investigated the effects of Tl (10–100 µM) on the viability and proliferation capacity of the adherent variant of PC12 cells (PC12 Adh cells). While both Tl(I) and Tl(III) halted cell proliferation from 24 h of incubation, their viability was ~ 90% even after 72 h of treatment. At 24 h, increased levels of γH2AX indicated the presence of DNA double-strand breaks. Simultaneously, increased expression of p53 and its phosphorylation at Ser15 were observed, which were associated with decreased levels of p-AKT^Ser473 and p-mTOR^Ser2448. At 72 h, the presence of large cytoplasmic vacuoles together with increased autophagy predictor values suggested that Tl may induce autophagy in these cells. This hypothesis was corroborated by images obtained by transmission electron microscopy (TEM) and from the decreased expression at 72 h of incubation of SQSTM-1 and increased LC3β-II to LC3β-I ratio. TEM images also showed enlarged ER that, together with the increased expression of IRE1-α from 48 h of incubation, indicated that Tl-induced ER stress preceded autophagy. The inhibition of autophagy flux with chloroquine increased cell mortality, suggesting that autophagy played a cytoprotective role in Tl toxicity in these cells. Together, results indicate that Tl(I) or Tl(III) are genotoxic to PC12 Adh cells which respond to the cations inducing ER stress and cytoprotective autophagy.

铊 (Tl) 及其两种阳离子 Tl(I) 和 Tl(III) 对大多数生物有毒。在这项工作中，我们研究了 Tl (10–100 µM) 对 PC12 细胞贴壁变体（PC12 Adh 细胞）的活力和增殖能力的影响。虽然 Tl(I) 和 Tl(III) 从孵育 24 小时起就停止了细胞增殖，但即使在处理 72 小时后，它们的存活率仍约为 90%。 24 小时时，γH2AX 水平升高表明存在 DNA 双链断裂。同时，观察到 p53 表达增加及其 Ser15 磷酸化，这与 p-AKT ^Ser473和 p-mTOR ^Ser2448水平降低相关。 72小时时，大细胞质空泡的存在以及自噬预测值的增加表明T1可能在这些细胞中诱导自噬。这一假设得到了透射电子显微镜 (TEM) 获得的图像以及 SQSTM-1 孵育 72 小时表达量下降和 LC3β-II 与 LC3β-I 比率增加的证实。 TEM 图像还显示内质网增大，加上 48 小时孵育后 IRE1-α 表达增加，表明 Tl 诱导的内质网应激先于自噬。用氯喹抑制自噬通量增加了细胞死亡率，表明自噬在这些细胞的 T1 毒性中发挥了细胞保护作用。总之，结果表明 Tl(I) 或 Tl(III) 对 PC12 Adh 细胞具有基因毒性，PC12 Adh 细胞对诱导 ER 应激和细胞保护性自噬的阳离子做出反应。