Evidence for chromosome instability in vivo in Bloom syndrome: increased numbers of micronuclei in exfoliated cells.

The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS) cells proliferating in vitro also occurs in vivo, and as part of a broad survey of various cancer-prone populations, to determine whether estimating micronucleus frequencies in exfoliated cell samples might be useful for identifying individuals with genetically determined chromosome instability. Eight individuals homozygous (bl/bl) for the BS gene, i.e., persons with the clinical syndrome, were examined, along with 11 obligate heterozygotes (bl/+), parents of affected persons. Exfoliated cells were obtained from two sites, the oral cavity and the urinary tract. Striking and statistically highly significant elevations in the frequencies of cells with micronuclei were observed in cells from both sites in bl/bl individuals compared to that in bl/+ (P less than 0.001) and in a control population, indicating that chromosome instability occurs in vivo in BS. In contrast, micronucleus frequencies at either site did not differ significantly between bl/+ individuals and the control population. This survey, in combination with similar earlier ones of populations predisposed to cancer not on a genetic basis but because of exposure to some environmental carcinogen, suggests that the exfoliated cell micronucleus test identifies individuals whose somatic genetic material has, for either genetic or environmental reasons, been damaged in a way that produces chromosome breakage and rearrangement.