Low dose tritiated water induced radiation-adaptive responses in lung cancer cells based on the Nrf2 pathway
This study investigated the induction of radiation adaptive response and its high activity threshold by tritiated water(HTO)in human non-small cell lung cancer cells(A549).The role of the Nrf2 pathway in the induction of adaptive response by HTO was further explored.Five gradient activities of HTO(7×103,1.4×104,2.1×104,2.8×104,3.5×104 Bq/mL)were set(accumulated radiation dose ranging from 0.55 to 8.27 mGy).A549 cells were pre-treated with HTO for 24 hours,followed by irradiation with 4 Gy X-rays.Cell viability was measured using MTT assay.The results showed that lower activities of HTO(7×103 and 1.4×104 Bq/mL)could restore the cell viability of A549 cells after 4 Gy irradiation,indicating the presence of an adaptive response.However,HTO with activities higher than 2.1×104 Bq/mL resulted in no recovery of cell viability in A549 cells,indicating the disappearance of adaptive response.Moreover,with increasing activity,cell viability further decreased.Considering that the adaptive response induced by HTO with an activity of 1.4×104 Bq/mL is the most significant,this activity of HTO was selected for the detection of oxidative levels.The results showed that HTO can significantly reduce the intra-cellular reactive oxygen species(ROS)levels after high-dose X-ray irradiation,indicating that the adaptive response is regulated by oxidative levels.Moreover,the addition of Nrf2 inhibitor(ML385)during the pre-treatment stage of HTO(1.4×104 Bq/mL)can significantly inhibit the radiation resistance induced by HTO,suggesting the involvement of the antioxidant pathway Nrf2 in this process.
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