Radiation carcinogenesis.
Research on radiation carcinogenesis during the past 2 decades has focused on cellular and molecular mechanisms for the effects of radiation in mammalian cells. This paper will review several of these areas of research, as they may relate specifically to the induction of cancer by ionizing radiation. Knowledge of the critical DNA damage of biologic importance, and how this damage is repaired, will be discussed in relation to its role in the induction of mutations by radiation. The search for the initiating event in radiation carcinogenesis, as well as other genetic events that may be involved, is discussed in terms of the possible role of the activation of oncogenes or tumor suppressor genes and the loss of cell-cycle checkpoints. Finally, evidence will be described indicating that important genetic consequences of radiation may arise in cells that in themselves receive no direct nuclear irradiation. It has been shown that radiation can, by itself, induce a type of genomic instability in cells, which enhances the rate at which mutations and other genetic changes arise in the descendants of the irradiated cell after many generations of replication. Preliminary evidence has been presented that irradiation targeted to the cytoplasm yields a significant increase in the frequency of mutations. Finally, genetic events including the induction of mutations and changes in gene expression may occur in neighboring cells that receive no direct radiation exposure at all. This 'bystander effect' involves gap junction mediated cell-cell communication, and activation of the p53 damage response pathway. The possible role of these phenomena in radiation carcinogenesis is discussed.
Little
J B
JB
Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. jlittle@hsph.harvard.edu
D000818:Animals; D002467:Cell Nucleus / Q000528:radiation effects; D003593:Cytoplasm / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D006801:Humans; D016296:Mutagenesis; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011839:Radiation, Ionizing
D004247:DNA