Heterogeneity in the clastogenic response to X-rays in lymphocytes from ataxia-telangiectasia heterozygotes and controls.
A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the yields of X-ray-induced breaks observed were within the higher mode of the distribution. However, lymphocytes from A-T heterozygotes sensitive to the induction of chromatid breaks by 60 cGy did not contain increased numbers of aberrations following exposure to 20 cGy. The radio-resistant inhibition of DNA synthesis that occurs in A-T homozygotes was not observed in heterozygotes. Co-cultivation experiments showed an increased G2 delay in lymphocytes from an A-T heterozygote whose lymphocytes contained increased X-ray-induced chromatid breaks. The results show a significant association of A-T heterozygosity with G2 chromosomal sensitivity (P less than 0.001; Wilcoxon rank sum test). The measurement of X-ray-induced breaks, however, failed to identify 37 percent of A-T heterozygotes tested. The predicted prevalence of increased sensitivity to X-rays in controls is approximately three- to 30-fold greater than the estimated frequency of A-T heterozygotes in the general population. Therefore, although the increased sensitivity to X-ray-induced chromatid breaks appears to be associated with the A-T-gene, it is not a reliable indicator of A-T heterozygosity. Genetic or environmental factors other than the A-T gene also must be involved in the increased clastogenic response.
Wiencke
J K
JK
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143-0560.
Wara
D W
DW
Little
J B
JB
Kelsey
K T
KT
D001260:Ataxia Telangiectasia / Q000097:blood / Q000150:complications / Q000235:genetics*; D002842:Chromatids / Q000528:radiation effects*; D002869:Chromosome Aberrations / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005069:Evaluation Studies as Topic; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D012307:Risk Factors; D012680:Sensitivity and Specificity