Abstract: Objective To investigate the effect of radiation-induced bystander effect on donor bone marrow cells during bone marrow transplantation and the protective effect of aryl hydrocarbon receptor (AHR) inhibitor CH223191 on donor bone marrow cells. Methods The mice were divided into 9 Gy irradiated group and 12 Gy irradiated group. The same number of donor bone marrow cells were transplanted after different radiation doses. The total number of peripheral blood cells, chimerism rate and number of peripheral blood donor cells were detected by flow cytometry. Serum reactive oxygen species (ROS) level of unirradiated mice and irradiated mice were detected by ELISA. The donor bone marrow cells were divided into control group, 9 Gy irradiated group and 12 Gy irradiated group and were cultured in vitro. Unirradiated mouse serum, 9 Gy and 12 Gy irradiated mouse serum were added for treatment, respectively. ATP activity assay was used to detect cell vitality, and flow cytometry was used to detect cell apoptosis. The mRNA expression of Cyp1a1 and Cyp1b1 was detected by RT-qPCR. Bone marrow cells treated with irradiated serum were divided into CH223191 treatment group and control group. After adding CH223191 treatment, cell viability, cell apoptosis and intracellular ROS levels were compared, and mRNA expression of Cyp1a1 and Cyp1b1 was detected by RT-qPCR. Bone marrow transplantation mice were divided into CH223191 treatment group and control group. In the treatment group, CH223191 was injected intraperitoneally. The body weight, chimerism rate and number of peripheral blood donor cells, chimerism rate and number of donor cells in bone marrow were recorded. Results The total number of peripheral blood cells in the 12 Gy irradiated group was less than that in the 9 Gy irradiated group (P＜0.05), whereas there was no significant difference in the chimeric rate of peripheral blood donor cells after bone marrow transplantation. However, the number of peripheral blood donor cells in the 12 Gy irradiated group was significantly less than that in the 9Gy irradiated group (P＜0.05).The serum ROS level increased after irradiation (P＜0.01). The activity of donor bone marrow cells was decreased and the percentage of apoptosis was increased (all P＜0.01), and the mRNA of Cyp1a1 and Cyp1b1 were increased in irradiated mouse serum (P＜0.05). After CH223191 was added into donor bone marrow cells treated with irradiated mouse serum, the mRNA levels of Cyp1a1 and Cyp1b1 were decreased (P＜0.05), the cell viability was increased, the intracellular ROS level was decreased, and the percentage of cell apoptosis was decreased (all P＜0.01). After bone marrow transplantation, mice in CH223191 treatment group lost less body weight compared with control group, the chimeric rate and cell number of peripheral blood donor cells were higher than control group, and the proportion and number of donor cells in bone marrow were higher than control group (all P＜0.05). The total counting of peripheral blood cells in the 12 Gy irradiated group was less than that in the 9 Gy irradiated group (P＜0.05), whereas there was no significant difference in the chimeric rates. Conclusions CH223191 inhibits the activation of AHR, reduces the damage of radiation-induced bystander effect on transplanted bone marrow cells, and improves the effect of bone marrow transplantation in mice.

Key words: bone marrow transplantation, radiation-induced bystander effect, aromatic hydrocarbon receptor, reactive oxygen species