Canadian Cytogenetic Emergency network (CEN) for biological dosimetry following radiological/nuclear accidents.

PURPOSE: To test the ability of the cytogenetic emergency network (CEN) of laboratories, currently under development across Canada, to provide rapid biological dosimetry using the dicentric assay for triage assessment, that could be implemented in the event of a large-scale radiation/nuclear emergency. MATERIALS AND METHODS: A workshop was held in May 2004 in Toronto, Canada, to introduce the concept of CEN and recruit clinical cytogenetic laboratories at hospitals across the country. Slides were prepared for dicentric assay analysis following in vitro irradiation of blood to a range of gamma-ray doses. A minimum of 50 metaphases per slide were analyzed by 41 people at 22 different laboratories to estimate the exposure level. RESULTS: Dose estimates were calculated based on a dose response curve generated at Health Canada. There were a total of 104 dose estimates and 96 (92.3%) of them fell within the expected range using triage scoring criteria. Half of the laboratories analyzed 50 metaphases in

Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans.

The biological effects of exposure to radioactive fluorodeoxyglucose ((18)F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo (18)F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of (18)F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of (18)F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual's radiation response. In summary, the results of this study indicate(18)F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.

Characterization of human embryonic stem cells with features of neoplastic progression.

Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced 'stemness'. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor-initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization reveals an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells.

Prenatal cytogenetic assessment and inv(2)(p11.2q13).

OBJECTIVES: To present a series of prenatally detected cases of recurrent pericentric inversions with euchromatic breakpoints and to review the literature to determine whether parental karyotyping is required for genetic counselling. METHODS: Cases of recurrent pericentric inversions with euchromatic breakpoints were collected from Canadian Cytogenetic Laboratories. Cases included inversions for chromosome 1(p13q21), chromosome 2(p11.2q13), chromosome 5(p13q13) and chromosome 10(p11.2q21.2). RESULTS: The incidence of de novo inv(2)(p11.2q13) was low, with one case among 91 inversions. There were no cases of de novo inv(10) (p11.2q21.2) among 17 reported and one case of de novo inv(5)(p13q13) among 21 reported. CONCLUSION: Our study, and data from the literature, suggests that most cases of inv(2)(p11.2q13) have been stably inherited, that de novo cases of inv(2) are rare and that both inherited and de novo forms are without phenotypic or developmental consequences. We suggest that parental karyotyping for cases of inv(2) is not useful in counselling as it may generate unnecessary parental anxiety over a chromosomal finding that is likely innocuous.