Suppressive effect of ascorbic acid on the mutagenesis induced by the bystander effect through mitochondrial function

Area of Science:

• Cell biology
• Radiation biology
• Biochemistry

Background:

• The radiation-induced bystander effect (RIBE) involves non-targeted cells responding to radiation exposure.
• Mitochondrial dysfunction and increased reactive oxygen species (ROS) are implicated in RIBE.
• Gene mutations can be induced by cellular stress, including that from RIBE.

Purpose of the Study:

• To investigate the suppressive effect of ascorbic acid (AsA) on mitochondrial changes and mutagenesis induced by RIBE.
• To determine if AsA can mitigate the cellular damage associated with RIBE.
• To elucidate the role of ROS in RIBE-induced mutagenesis and AsA's protective mechanism.

Main Methods:

• Mammalian cell lines were used for medium transfer assays.
• Conditioned medium from X-irradiated cells was applied to recipient cells to induce RIBE.
• Mitochondrial membrane potential and superoxide radical levels were measured.
• Gene mutations were assessed.
• The effects of ascorbic acid (AsA) treatment were evaluated.

Main Results:

• Conditioned medium from irradiated cells altered mitochondrial membrane potential and increased mitochondrial superoxide radical (O2(-)) levels in recipient cells.
• Increased ROS levels correlated with the induction of gene mutations.
• Ascorbic acid (AsA) completely suppressed the mitochondrial modulations and mutation induction caused by RIBE.
• These protective effects were observed in cells treated with conditioned medium.

Conclusions:

• Secreted factors mediate the radiation-induced bystander effect (RIBE), leading to mitochondrial dysfunction and mutagenesis.
• Reactive oxygen species (ROS), particularly those localized in mitochondria, play a key role in RIBE-induced gene mutations.
• Ascorbic acid (AsA) effectively suppresses RIBE-induced mitochondrial changes and mutagenesis, suggesting its potential as a radioprotective agent.