The rate of chromosomal breakage in response to mitomycin C, ethylmethanesulfonate, methylmethanesulfonate, X-rays, and 5-bromodeoxyuridine has been measured by the production of micronuclei. Micronuclei arise from chromosomal fragments that are not incorporated into daughter nuclei because they lack kinetochores. Four groups of people were studied: patients with Fanconi's anemia; carriers of the Fanconi's anemia gene; normal controls; and a patient with an aplastic anemia of unknown origin. Patients with Fanconi's anemia are easily identified by the micronucleus technique on the basis of: (a) an elevated spontaneous frequency of micronuclei corresponding to the elevated spontaneous aberration rate; and (b) the elevated production of micronuclei after mitomycin C treatment corresponding to the increased sensitivity to chromosomal breakage by cross-linking agents. These features permit a rapid confirmation of the diagnosis without the need for the more difficult metaphase analysis of chromosomes. None of the other groups differed significantly in response to mitomycin C or to the other mutagens used. Cells of Fanconi's anemia were no more sensitive to the other agents than were cells of normal controls, except for a slight increase in X-ray sensitivity.
Supported by grants from the Atkinson Charitable Foundation, the National Cancer Institute of Canada, and the National Research Council of Canada.