Abstract
We are living in the environment with numerous natural and man-made chemicals that are cancer-initiating and promoting potentials. For this reason, radiation carcinogenesis in human is considered as a result of interaction with these factors. But, the quantitative assessment and mechanistic understanding of combined effects of radiation and chemical carcinogens are still insufficient. Murine thymic lymphoma (TL), which are reproducibly induced by radiation and chemicals, has been utilized as a good model for elucidating cellular and molecular mechanism of human lymphocytic leukemia. The aim of this study are (i) to determine the mode of TL induction by combined treatment of X-rays and N-ethyl-N-nitrosourea (ENU), and (ii) to compare the molecular alterations among the TLs induced after X-rays, ENU or combined treatment. The dose-response curve of TLs after single treatment of X-rays and ENU was sigmoidal and linear, both with threshold dose, respectively. For combined treatment, synergistic effect was obvious for high dose radiation, while the effect was marginal for low or threshold dose radiation. It was interesting that there still existed threshold for X-rays in the combination with ENU. The molecular changes in the TLs induced by combined treatment were similar to those by ENU. It is suggested, therefore, that radiation acts as promoter or conditioner for ENU-induced lymphomagenesis.
