Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition.
Sanford et al. (Int. J. Radiat. Biol. 55, 963-981, 1989) have reported that G2-phase cells from many heritable cancer-prone conditions exhibit higher yields of X-ray-induced chromosome damage than those found in the majority of healthy controls. We have applied their protocol to lymphocytes of a group of control and cancer-prone individuals to see if we could confirm these observations. For control donors we observed higher aberration yields, different kinetics and more interexperiment variability than found by Sanford et al. These differences could not be attributed to unavoidable minor variations in procedures (e.g. serum batches, glassware washing methods), but the difference in X-ray qualities used in the two laboratories may have made a small contribution to the discrepancies. We attribute some of our experimental variability to the fact that, to varying extents in different experiments, centrifugation of cells prior to irradiation can slow down the progression of cells into metaphase and that cells can continue to repair during the harvesting procedure (centrifugation and hypotonic treatment). We have applied the assay to cases of ataxia telangiectasia (AT, homozygotes and heterozygotes), xeroderma pigmentosum (homozygotes and heterozygotes), familial adenomatous polyposis and the syndromes Li-Fraumeni, basal cell nevus, Down's and Fanconi's but have been unable to discriminate between these groups and controls except for AT homozygotes. By including a control sample in parallel with samples from cancer-prone groups we found a significant difference in mean aberration yields between controls and AT homozygotes and heterozygotes, but not for the other groups. Since technical features could explain the discrepancies between our laboratories, we have devised our own G2-phase assay which appears to be giving promising results.
Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, United Kingdom.
D
D
Scott
A R
AR
Spreadborough
L A
LA
Jones
S A
SA
Roberts
C J
CJ
Moore
D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000293:Adolescent; D001260:Ataxia Telangiectasia / Q000235:genetics; D001478:Basal Cell Nevus Syndrome / Q000235:genetics; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects*; D004198:Disease Susceptibility; D004314:Down Syndrome / Q000235:genetics; D005134:Eye Neoplasms / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics; D005260:Female; D016195:G2 Phase; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D007223:Infant; D007700:Kinetics; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance; D012016:Reference Values; D012208:Rhabdomyosarcoma / Q000235:genetics; D013997:Time Factors; D014430:Twins, Monozygotic; D014965:X-Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics