The use of X-rays for medical diagnosis is enhancing exposure to low radiation doses. Exposure to extremely low-frequency electromagnetic or magnetic fields is also increasing. Epidemiological studies show consistent associations of childhood leukaemia with exposure to magnetic fields but any causal relationship is unclear. A limitation in assessing the consequence of such exposure is the availability of sensitive assays. The embryonic neuronal stem and progenitor cell compartments are radiosensitive tissues. Using sensitive assays, we report a statistically significant increase in DNA double-strand break (DSB) formation and apoptosis in the embryonic neuronal stem cell compartment following in utero exposure to 10–200 mGy X-rays. Both endpoints show a linear response. We also show that DSB repair is delayed following exposure to doses below 50 mGy compared with 100 mGy. Thus, we demonstrate in vivo consequences of low-dose radiation. In contrast to these impacts, we did not observe any significant induction of DSBs or apoptosis following exposure to 50 Hz magnetic fields (100 or 300 µT). We conclude that any DSB induction by treatment with magnetic fields is lower than following exposure to 10 mGy X-rays. For comparison, certain procedures involving computed tomography scanning are equivalent to 1–5 mGy X-rays.

Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of γH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (γH2AX, 53BP1 and RAD51) in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-2′-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy. After 10 months, the lens aspect ratio was also altered, an indicator of the consequences of the altered cell proliferation and cell density changes. A best-fit model demonstrated a dose-response peak at 500 mGy. These data identify specific nonlinear biological responses to low (less than 1000 mGy) dose IR-induced DNA damage in the lens epithelium.

. FAP patients inherit a mutated copy of the adenomatous polyposis coli (APC) gene (1-3), whereas hereditary nonpolyposis CRC is caused by inheritance of defective DNA mismatch repair genes such as MSH2 or MLH1 (4, 5). However, hereditary nonpolyposis CRC and FAP account for only a small fraction of the colorectal tumors presenting in the human population. The vast majority of CRCs (Ϸ80%) do not result from a known inherited factor, are considered sporadic in origin, and demonstrate somatic mutation of the APC gene (6-10).Many studies have suggested a role for uncharacterized genetic factors in predisposition to the common forms of colorectal tumors. Thus, relatives of CRC patients are at an increased risk of the disease, and segregation analysis has suggested dominant inheritance of CRC susceptibility (11,12). In addition, an extensive analysis of twins showed that up to one-third of CRCs may have some inherited basis (13). The remaining, uncharacterized predisposition to CRC in humans is more likely to be the result of several genes of low-penetrance rather than highpenetrance mutations at single loci with large effects on risk (14). Much of the risk of CRC may result from a primary predisposition to colorectal adenomas. The number of colorectal adenomas presenting within FAP families or individuals with identical germ-line APC mutations has been shown to vary, suggesting that hereditary factors also may influence disease severity (15). The same genes that modify the phenotype of individuals with FAP also may influence the risk of CRC in the general population. A search for FAP modifier genes, either directly or through rodent models, therefore may lead to the identification of important susceptibility genes for human CRC.The first mouse model used to study the involvement of the Apc gene in CRC is referred to as Min (Multiple intestinal neoplasia). Apc Min/ϩ (Min) mice are heterozygous for a truncating Apc mutation and develop numerous intestinal adenomas, thereby providing a good model of human FAP. The Min model has been used to provide an unambiguous example of a modifying locus in mice. A single locus was identified as a consequence of significant variation in the polyp number, depending on the inbred mouse strain harboring the Apc mutation. Linkage analysis located Mom1 on mouse chromosome 4, and further analysis identified the secretory phospholipase A2 (Pla2g2a) as a candidate gene (16)(17)(18). Unfortunately, studies in humans did not confirm PLA2G2A as a major modifier of colorectal cancer risk in humans because functional polymorphic variation did not exist (19,20). A second locus, Mom2, on distal chromosome 18 was identified by Silverman et al. (21), although the underlying genetic defect has yet to be established. We now have direct evidence of a further Mom locus controlling susceptibility to a particularly severe form of intestinal disease in Min mice. Materials and MethodsHusbandry. Mice were housed in conventional cages, and a standard maintenance diet was provided ad libitum. All procedures i...