Ex: Side effects caused by cancer radiotherapy Radiation-Induced Bystander Effects (RIBE) Effects seen in unexposed cells that are adjacent to or far away from the irradiated cells Ex: Side effects caused by cancer radiotherapy (hair loss, low blood cells, skin irritation, and cancer in nearby tissues) unexposed cells receiving bystander signal “Radiation-induced bystander effect and DNA damage” Jalal, N. et al. Journal of Cancer Research and Therapeutics 2014

X-ray treatment of tuberculosis Short History of RIBE William Roentgen: Discoverer of X-rays X-ray treatment of tuberculosis

Irradiation of spleen results in significant decrease in bone marrow cells “Changes in sternal bone marrow following roentgen-ray therapy to the spleen in chronic granulocytic leukaemia” Parsons, W.B. Cancer (1954)

Chromosomal abnormalities seen in normal cells treated with plasma from irradiated patients A. Chromatid Break C. Quadriradial chromatid exchange figure B. Dicentric chromosomes D. Translocated chromosome F. Chromosome clumping E. Chromosome and isochromatid breaks; acentric fragments “Chromosome Damage Induced by Plasma of X-Rayed Patients: An Indirect Effect of X-Ray” Hollowell and Littlefield. PSEBM (1968)

Increased frequency of Sister Chromatid Exchanges in unexposed cells <1% of cells irradiated with very low dose of 𝓪-particles -> 30% of cells experienced SCE RIBE is a low dose phenomenon “Induction of Sister Chromatid Exchanges by Extremely Low Doses of a-Particles” Nagasawa and Little. Cancer Research (1992)

The nature of the RIBE factors is unknown Radiation Genome instability Cell proliferation Factors? Survival or death Gene expression irradiated cell non-irradiated cell Adaptive responses Important for: - Minimizing side effects in cancer radiotherapy - Radiation safety and radioprotection

(e.g. Y-H2A.X Immunostaining) Medium transfer system to study RIBE HepG2, HeLa, huh-7 HEK 293T Bystander responses (e.g. Y-H2A.X Immunostaining)