Radiation quality effects alteration in COX-2 pathway to trigger radiation-induced bystander response in A549 lung carcinoma cells

Abstract

This study aimed to determine whether the radiation-induced bystander effect (RIBE) is affected by radiation quality. To mimic the different radiation qualities of the direct action (D)/indirect action (ID) ratio, A549 cells were exposed to X-rays, with either 100 mM of the radical scavenger, thio-urea (TU⁺), or null (TU^–). Biological responses in irradiated and bystander cells were compared at equal lethal effects of a 6% survival dose, which was estimated from the survival curves to be 8 Gy and 5 Gy for TU⁺ and TU^–, respectively. Cyclooxygenase-2 (COX-2) expression in TU^– irradiated cells increased up to 8 h post-irradiation, before decreasing towards 24 h. The concentration of prostaglandin E2 (PGE₂), a primary product of COX-2 and known as a secreted inducible factor in RIBE, increased over 3-fold compared with that in the control at 8 h post-irradiation. Conversely, COX-2 expression and PGE₂ production of TU⁺ irradiated cells were drastically suppressed. These results show that the larger D/ID suppressed COX-2 expression and PGE₂ production in irradiated cells. However, in contrast to the case in the irradiated cells, COX-2 expression was equally observed in the TU^– and TU⁺ co-cultured bystander cells, which showed the highest expression levels at 24 h post-irradiation. Taken together, these findings demonstrate that radiation quality, such as the D/ID ratio, may be an important factor in the alteration of signalling pathways involved in RIBE.