Mechanisms of chromatid breaks
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Individuals have widely differing radiosensitivities as shown in the G2 radiosensitivity experiments in blood lymphocytes from conditions such as breast cancer and ataxia telangiectasia (AT) (Sanford et al 1989, Scott et al 1994, 1996)). This study investigated whether there was a correlation in colour switch ratio (the number of colour-switch breaks/total number of breaks) and radio sensitivity in breast cancer and normal surgical controls and in an AT and normal lymphoblastoid cell line. Harlequin-stained cells were subjected to the G2 assay and the number of chromatid breaks in the light and dark strands and colour-switch breaks were scored in 100 cells per sample. The mean csr in breast cancer patients was 25.8% compared to a mean of 15.9% in control patients indicating a, significant difference; P= 0.0024. The mean radiosensitivity (which was expressed as the frequency of chromatid breaks/100 cells) in breast cancer patients (56.2) was also significantly higher than the mean radio sensitivity in control patients (27.9); P= 0.0000. When csr was plotted against radiosensitivity, two separate cohorts were produced - one for breast cancer individuals and a second for control individuals suggesting a possible use in breast cancer screening. In the AT cell line, however, the mean csr was 29% compared to the mean of 26% in the normal control cell line. There was thus no significant difference in csr between the AT and normal cell line; P= 0.13. It might be expected that as AT individuals are hypersensitive to ionising radiation (as indicated by the higher number of chromatid damage), they might (if csr was related to radiosensitivity) have a significantly higher csr than normal or breast cancer patients. From the results presented, however, this appears not to be the , case. The results indicate that csr and radiosensitivity are not always correlated. Thus the results show that although csr and radiosensitivity are not always correlated in the AT cell line investigated, when radiosensitivity was plotted against csr, the breast cancer cohort appeared to separate from the control patients. It was very interesting to observe that in this study, all of the breast cancer individuals were discriminated by this correlation of high csr and radiosensitivity in comparison to normal control individuals. If this correlation is confirmed in several more studies, this predictive test has the potential to be used as an assay to detect individuals predisposed to breast cancer. If it discriminates almost all of the breast cancer cases as my experiments showed, then this could prove to be a more valuable and accurate assay than the G2 assay which has been shown to discriminate 42% radiosensitive breast cancer patients (Scott et al 1994).
Thesis, PhD Doctor of Philosophy
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