Biomarkers for low-level exposure causing epigenetic responses in stem cells.

Our current understanding of experimental in vitro and in vivo studies, as well as of epidemiological data, suggests that carcinogenesis is the result of many endogenous and exogenous factors interacting during a multi-step, multi-mechanism process. No single factor "causes" cancer. Carcinogenesis is known to involve both mutagenic and nonmutagenic processes. Therefore, the objective of this review is to examine how low dose exposure to ionizing radiation might contribute to the carcinogenic process and if measurable "biomarkers" might be used to monitor the susceptibility, exposure, biological consequence and clinical disease patterns attributable to ionizing radiation. While the primary biomarker for ionizing radiation has been DNA damage and genetic/chromosomal mutations, possible effects on apoptosis and epigenetic processes have been examined. The search for biomarkers of cytotoxic (apoptotic) and epigenetic events induced by low-level ionizing radiation was thought to be difficult in view of the fact that controlled apoptotic and epigenetic events occur constantly in a healthy body exposed to background radiation. In addition, if the stem cell is the target cell for low-level radiation exposure, detection of biomarkers in this small subpopulation of cells in any tissue places severe limitations on any practical noninvasive means to identify such biomarkers. Last, a critical re-examination of the cancer incidence data of the Hiroshima/Nagasaki A-bomb survivors is suggested in view of modifying factors such as caloric restriction and post-irradiation trauma/treatment that could affect the multi-stage nature of carcinogenesis.