Abstract
It has long been assumed that DNA damage induced by radiation is directly involved in carcinogenesis. In this direct hypothesis, DNA damage is fixed as carcinogenic mutation in a irradiated cells within a short period of time after the exposure. However, it is known that some cancer has a long latency which could suggest that carcinogenic mutation is induced not at the time but a long time after exposure to radiation. In addition, we still do not have a direct proof that irradiated cells are the actual target of radiation carcinogenesis. Recent advances of radiation biology have excavated a series of biological responses which may have an important implication in radiation carcinogenesis. Genomic instability induces mutation not in the directly irradiated cells, but in their descendant through the indirect mechanism. Bystander effect induces mutation not in the irradiated cells but in the surrounding cells. In addition to these cellular radioresponses, the tissue level regulations in a body form yet another dimension when one consider the mechanism of radiation carcinogenesis. For example, the current radiation protection system assumes that radiation doses given at a low dose rate can be summed up to give cumulative dose on which radiation risk is evaluated. However, cells in a tissue are constantly turning over and for most of the cells, the summation of the doses is possible as long as the target cells are not discarded from the body. The above mentioned cellular and tissue mechanisms complement the epidemiological data on radiogenic cancer in human to better understand the mechanism of radiation carcinogenesis. For example, the linear increase of the solid tumors among atomic bomb survivors is in contradiction with the multistep mechanism of carcinogenesis if radiation functions as a direct carcinogen. However, the linearity can be explained if carcinogenic mutation is induced by genomic instability. Another example is the temporal pattern of the relative risk decline among atomic bomb survivors which might better be explained by the loss of the initiated target cells in the tissue. In the past, the two disciplines of the radiation carcinogenesis field, molecular/cellular/tissue radiation biology and epidemiology have worked independently. However, new discoveries made in the recent years on both sides are rich enough to complement each other. Thus, the time is ripe to have this symposium in which the two come together to discuss the important issue to better understand the biological mechanism and the risk of radiation carcinogenesis.
