Abstract
The assessment of chromosomal mutations in children may provide information about aetiology and risk of second malignancies. A somatic cell mutation assay which determines variant erythrocytes lacking expression of an allelic form of the sialoglycoprotein, glycophorin A, was applied to samples from children before and after receiving potentially genotoxic therapy. Fifty-six children who had received treatment for their malignancy, 15 with malignancy but prior to treatment and 43 control children were assessed for the presence of Nø and NN mutant variant red cells. Control children had mean (s.d.) Nø and NN variant frequencies (Vf) of 9.5 (7.0) and 5.8 (3.3) x 10(6) erythrocytes respectively. Comparison between pre-treatment and control groups demonstrated that prior to chemotherapy, patients with paediatric malignancy do not have mutant frequencies significantly different from the normal population. Children who had received chemotherapy, with or without radiotherapy, showed a significant elevation of both Nø and NN variants over 10 years from the end of treatment. Exposure of children to radiotherapy or known chemical mutagens leads to an increased frequency of variant erythrocytes which is probably the result of in vivo somatic cell mutations. The long term implications have yet to be determined.
Highlights
Linear regression analysis of the N0 variant frequencies (Vf) against age in the control group did not suggest a positive relationship in this group of children
Both mN0 and mNN variant values were plotted against time elapsed from the end of chemotherapy (Figures 2 and 3)
Variant frequencies rose through the latter parts of some of the prolonged courses of chemotherapy but fell towards normal over the subsequent years
Summary
Patients and samples Samples of blood for both control and study groups were obtained from children attending the Royal Hospital for Sick Children, Bristol or regionally supported clinics. Forty-three children (mean age 6.3 years; range 0.9-16.4 years) attending the hospital for routine surgery provided control samples. In 15 of the patient group, the samples were obtained before chemotherapy was started (mean age 5.4 years; range 1.6 - 16.6 years) and these children are referred to as the pretreatment group. Fifty-six patients with paediatric malignancies (mean age 13.4 years; range 2.2-32.9 years) provided samples 1 to 16.5 years after diagnosis. These children, who were aged 0.93 to 16.58 years at the time of diagnosis, formed the post-treatment group. No child in this part of the study provided more than one sample. The study was approved by the Bristol and Weston Health Authority Ethical Committee
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