Radiation Kills - Bystander effects now abundantly confirmed . . . 

Bystander effects now abundantly confirmed    
Since then, a wide range of bystander effects in cells not directly exposed to   
ionizing radiation have been found, which are the same as or similar to those in   
the cells that were exposed [4], including cell death and chromosomal   
instability.     Actually, radiation induced bystander effects have been described as far back as   
1954, when factors that cause damage to chromosomes could be detected in the   
blood of irradiated patients. Carmel Mothersill and Colin Seymour at McMaster   
University published a key paper in 1997 showing that filtered medium from   
irradiated human epithelial cells can reduce the survival of unirradiated cells,   
suggesting that soluble factors produced by the irradiated cells were involved   
in the bystander effects [5].     
Indeed, serum from cancer patients treated with radiotherapy also causes cell   
death and chromosomal instability in unexposed cells in culture, and this has   
been shown as far back as 1968 [6].     
In 2001, researchers at Columbia University, New York used microbeams to target   
single cells with exactly defined numbers of a-particles. They found that   
hitting 10 % of the cells induced the same frequency of cancerous transformation   
as when every cell in the dish was targeted [7].     
More recently, bystander DNA double-strand breaks were induced in a three-  
dimensional human tissue culture that is closer to in vivo conditions. The   
results obtained by the team led by Olga Sedelnikova at the National Cancer   
Institute, Bethesda, Maryland, were much more dramatic. In marked contrast to   
cultured cells in two-dimensions where maximal DSB occurred 30 minutes after   
irradiation, the incidence of DSBs in bystander cells reached a maximum between   
12 to 48 hours after irradiation, gradually decreasing only over 7 days. At the  
 maximum, 40 to 60 % of cells were affected [8]. These increases in bystander   
DSBs were followed by increased apoptosis and micronucleus formation, loss of   
nuclear DNA methylation and increased fractions of senescent cells. The authors   
commented that treatment of primary tumours with radiation therapy frequently   
results in the growth of a secondary malignancy of the same or different origin.   
They raised the question on whether bystander effects could introduce negative   
complications in radiation therapy, such as genomic instability in normal   
tissues. They concluded that induced senescence might be a protective mechanism.   
On the other hand, failure of these protective pathways can lead to the   
appearance of proliferating, damaged cells and to an increased probability of   
oncogenic transformation.    
New research from the University of Pittsburgh Pennsylvania throws further light   
on the implications of bystander effects for radiotherapy. It is customary for  
 patients receiving bone-marrow transplant to undergo whole body irradiation to   
kill the bone marrow cells of the host so as to encourage repopulation by   
transplanted cells. The researcher found that irradiated mouse recipients   
significantly impaired the long-term repopulating ability of transplanted mouse   
haematopoietic stem cells (HSCs) 17 hours after exposure to irradiated hosts,   
and before the cells began to divide. There was an increase in acute cell death   
associated with accelerated proliferation of the bystander HSCs. The effect was   
marked by a dramatic down-regulation of c-Kit (a proto-oncogene), apparently   
because of elevated reactive oxygen species (ROS). Administration of an   
antioxidant chemical or ectopically over-expression of a ROS scavenging enzyme   
catalase improved the function of transplanted HSCs in the irradiated hosts [9].   
This obviously has implications for protecting patients during radiotherapy as   
well as those receiving bone-marrow transplant.     
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