Strong association between cancer and genomic instability.
After a first wave of radiation-induced chromosomal aberrations, a second wave appears 20-30 cell generations after radiation exposure and persists thereafter. This late effect is usually termed "genomic instability". A better term is "increased genomic instability". This effect has been observed in many cell systems in vitro and in vivo for quite a number of biological endpoints. The radiation-induced increase in genomic instability is apparently a general phenomenon. In the development of cancer, several mutations are involved. With increasing genomic instability, the probability for further mutations is enhanced. Several studies show that genomic instability is increased not only in the cancer cells but also in "normal" cells of cancer patients e.g. peripheral lymphocytes. This has for example been shown in uranium miners with bronchial carcinomas, but also in untreated head and neck cancer patients. The association between cancer and genomic instability is also found in individuals with a genetic predisposition for increased radiosensitivity. Several such syndromes have been found. In all cases, an increased genomic instability, cancer proneness and increased radiosensitivity coincide. In these syndromes, deficiencies in certain DNA-repair pathways occur as well as deregulations of the cell cycle. Especially, mutations are seen in genes encoding proteins, which are involved in the G(1)/S-phase checkpoint. Genomic instability apparently promotes cancer development. In this context, it is interesting that hypoxia, increased genomic instability and cancer are also associated. All these processes are energy dependent. Some strong evidence exists that the structure and length of telomeres is connected to the development of genomic instability.
Streffer
Christian
C
University-Clinics, Auf dem Sutan 12, 45239, Essen, Germany. streffer.essen@t-online.de
D000818:Animals; D004781:Environmental Exposure / Q000009:adverse effects; D042822:Genomic Instability / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*