Most radiation biologists/radiation oncologists have long accepted the concept 
that the biologic effects of radiation principally involve damage to 
deoxyribonucleic acid (DNA), which is the critical target, as described in 
"Radiobiology for the Radiologist", by E.J. Hall and A.J. Giaccia [1]. Although 
the concepts of direct and indirect effects of radiation are fully applicable to 
low-LET (linear energy transfer) radioresistant tumor cells/normal tissues such 
as osteosarcoma cells and chondrocytes, it is believed that radiation-associated 
damage to DNA does not play a major role in the mechanism of cell death in 
low-LET radiosensitive tumors/normal tissues such as malignant lymphoma cells 
and lymphocytes. Hall and Giaccia describe lymphocytes as very radiosensitive, 
based largely on apoptosis subsequent to irradiation. As described in this 
review, apoptosis of lymphocytes and lymphoma cells is actually induced by the 
"hydrogen peroxide (H₂O₂) effect", which I propose in this review article for 
the first time. The mechanism of lymphocyte death via the H₂O₂ effect represents 
an ideal model to develop the enhancement method of radiosensitivity for 
radiation therapy of malignant neoplasms. In terms of imitating the high 
radiosensitivity of lymphocytes, osteosarcoma cells (representative of low-LET 
radioresistant cells) might be the ideal model for indicating the conversion of 
cells from radioresistant to radiosensitive utilizing the H₂O₂ effect. External 
beam radiation such as X-rays and high-energy electrons for use in modern 
radiotherapy are generally produced using a linear accelerator. We theorized 
that when tumors are irradiated in the presence of H₂O₂, the activities of 
anti-oxidative enzymes such as peroxidases and catalase are blocked and oxygen 
molecules are produced at the same time via the H₂O₂ effect, resulting in 
oxidative damage to low-LET radioresistant tumor cells, thereby rendering them 
highly sensitive to irradiation. In this review, this potential paradigm shift 
in modern radiation biology/radiation oncology is discussed in detail in terms 
of overcoming drug/radiation resistance in radiation therapy and/or anti-cancer 
chemotherapy.