Genomic instability and radiation effects

Complete text of publication follows. Cancer, genetic mutations and developmental abnormalities are apparently associated with an increased genomic instability. Such phenomena have been frequently shown in human cancer cells in vitro and in situ. It is also well-known that individuals with a genetic predisposition for cancer proneness, such as ataxia telangiectesia, Fanconi anaemia etc. demonstrate a general high genomic instability e.g. in peripheral lymphocytes before a cancer has developed. Analogous data have been found in mice which develop a specific congenital malformation which has a genetic background. Under these aspects it is of high interest that ionising radiation can increase the genomic instability of mammalian cells after exposures in vitro an in vivo. This phenomenon is expressed 20 to 40 cell cycles after the exposure e.g. by de novo chromosomal aberrations. Such effects have been observed with high and low LET radiation, high LET radiation is more efficient. With low LET radiation a good dose response is observed in the dose range 0.2 to 2.0 Gy, Recently it has been reported that senescence and genomic instability was induced in human fibroblasts after 1 mGy carbon ions (1 in 18 cells are hit), apparently bystander effects also occurred under these conditions. The instability has been shown with DNA damage, chromosomal aberrations, gene mutation and cell death. It is also transferred to the next generation of mice with respect to gene mutations, chromosomal aberrations and congenital malformations. Several mechanisms have been discussed. The involvement of telomeres has gained interest. Genomic instability seems to be induced by a general lesion to the whole genome. The transmission of one chromosome from an irradiated cell to an non-irradiated cell leads to genomic instability in the untreated cells. Genomic instability increases mutation rates in the affected cells in general. As radiation late effects (cancer, gene mutations and congenital malformations) develop by going through several mutation steps, an increase of genomic instability can have the consequence that the probability for the necessary mutation steps after the initiation processes will be enhanced and facilitated. In this connection it is of high interest that genomic instability is increased in several human populations who have developed or will develop a cancer with/or without radiation. The genomic instability was studied in peripheral lymphocytes of these patients. Such an effect has been found in patients with head and neck cancers before treatment. It has been observed in uranium miners and patients with Morbus Hodgkin who developed secondary cancers after exposures. The implications of these phenomena for low dose radiation seem to be important.