Implications of Stem Cell Radiobiology for Radiation- Induced Cancer Risk

摘要

The radiological protection system for cancer risk is based on a conceptual framework involving the linear-no-threshold and relative risk models, cancer risk differences among tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. Human epidemiological data for cancer incidence versus dose are used with the system to provide recommended dose limits in different situations. Cancer induction from radiation is a complex process involving mutations in target cells and various kinetic processes leading to malignancy. The identity of the target cells for carcinogenesis continues to focus mainly on the more-primitive and mostly-quiescent stem-cell population, able to accumulate the protracted sequence of mutations necessary to result in malignancy. Several biological processes could contribute in protecting stem cells from mutation accumulation: (1) accurate DNA repair, (2) rapid induced death of injured stem cells, (3) retention of the intact parental DNA strand during stem-cell divisions in some tissues so that mutations are side-lined to the daughter differentiating cells, and (4) stem-cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the microenvironmental stem-cell "niche". DNA repair operates mainly within a few days after irradiation, while stem cell renewal and competition requires weeks or many months depending on the tissue type. Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in "niches", and radiosensitivity to acute and protracted exposures, recently has been reviewed regarding hematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone, in order to provide a biological insight to protection issues.