Factors influencing chromosome aberration yields in the human peripheral leukocyte system.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M A Bender.
Explore the source record for details and available documents.
Contrary to an earlier report, peripheral lymphocytes from 4 AT patients were not found to exhibit higher yields of unequivocal chromosome type aberrations following irradiation in the G0 phase of the cell cycle, providing that only first post-irradiation metaphases were included in the samples (ensured by 5-bromodeoxyuridine (BrdU) incorporation and differential fluorescence or Giemsa staining). We were able, however, to confirm the earlier-reported increase in chromatid-type aberrations in the G0-irradiated cells. AT lymphocytes were found to experience more cell-cycle delay following G0 irradiation than normal cells. These observations appear consistent with the damaged base excision DNA-repair defect reported for AT cells.
Earlier work of several laboratories established that the yields of radiation-induced ring and dicentric chromosomes are greater when human peripheral blood lymphocytes are irradiated in GH1 some hours after phytohemagglutinin stimulation than if they are irradiated in G0 before stimulation. Post-treatment of lymphocytes irradiated in G0 with the DNA polymerase inhibitor aphidicolin, which is effective against both pol alpha and pol delta, produces a similar increase in ring and dicentric yield. We found that aphidicolin post-treatment was much less effective in increasing ring and dicentric yield increases in cells irradiated in G1 four to five hours after stimulation. Because we had earlier found specific inhibitors of DNA pol alpha ineffective in producing increased yields in either G0 or G1 lymphocytes, we conclude that much of the G0 to G1 increase in yields is mediated by pol delta.
We have examined the distributions both of spontaneous and X-ray-induced micronuclei (MN) and of spontaneous and UV-induced unscheduled DNA synthesis (autoradiographic grains; UDS) in cultures of peripheral blood lymphocytes from normal, healthy human volunteers. While the spontaneous MN and UDS do not differ significantly from the expected Poisson distributions, both the induced MN and UDS are strongly overdistributed (i.e., variance much greater than mean). This not only must be allowed for in statistical tests used for population monitoring, but offers suggestive evidence that there are large differences in radiation response from sample to sample, some of which may reflect true differences among normal, healthy subjects.
A lymphocyte clone with a 45, XY karyotype with a 14/14 tandem translocation marker, the frequency of which is time-variable, has been observed in an ataxia telangiectasia patient. Cells with the marker chromotosome were not observed in fibroblasts cultures derived from a skin biopsy, nor was the marker observed in leukocyte cultures from the patient's two affected sibs.
Explore the source record for details and available documents.