The assessment of in vivo somatic mutations in survivors of childhood malignancy.
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.
Hewitt
M
M
Department of Paediatric Oncology, Royal Hospital for Sick Children, Bristol, UK.
Mott
M G
MG
D000293:Adolescent; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D008951:MNSs Blood-Group System / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D013997:Time Factors
D000970:Antineoplastic Agents; D008951:MNSs Blood-Group System