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. Read the rest of this report on the ISIS website http://www.i-sis.org.uk/Bystander_Effects_Multiply_Dose.php
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