Lymphocyte DNA in Aplastic Anaemia

Using ultracentrifugation on alkaline sucrose density gradients the DNA of lymphocytes from 14 patients with aplastic anaemia and 23 controls was studied before and after exposure to bleomycin, an agent known to cause strand breaks in DNA. Before exposure to bleomycin the DNA from aplastic patients had more strand breaks than the DNA from the controls of similar ages. Following exposure to bleomycin an abnormal number of DNA strand breaks was produced in 10 of 14 patients and this molecular evidence of drug sensitivity correlated well with the sensitivity of the proliferating lymphocytes to bleomycin in tissue culture. Furthermore, two relatives of patients with aplastic anaemia showed similar abnormality of DNA before and after exposure to bleomycin and increased sensitivity to bleomycin in tissue culture. These results suggest that an abnormality of DNA structure and/or repair may be present in some patients with aplastic anaemia.