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Ultrastructural Alterations in Avian Leukemic Myeloblasts Exposed to Actinomycin D in Vitro¹

Department of Surgery, Duke University Medical Center, Durham, North Carolina

Ultrastructural studies were made of avian myeloblasts infected with BAI strain A avian tumor virus treated in tissue culture with actinomycin D (AD). The treated cells were examined in chronologically correlated studies on the influence of the antibiotic on myeloblast growth behavior and on the synthesis of cell and virus RNA. Most of the work was carried out with cultures containing about 10⁸ cells/ml and 0.5 µg AD/ml. Ultrastructural changes beginning within 1 hr of exposure consisted of nucleolar component rearrangement increasing in magnitude for about 6 hr without cell death or more than minor alterations in the cytoplasm. The characteristics of the changing nucleolar components were determined by digestion with nucleases and proteinases. Further exposure resulted in destruction of the nucleolus and progressive nuclear and cytoplasmic alterations associated with cell death and disintegration at levels proportional to exposure time. At 24 hr approximately 50% of the cells remained viable, but all exhibited nucleolar damage. The ultrastructural findings are discussed in relation to the results of the parallel biochemical studies.

¹ This work was aided by a research grant (C-4572) to Duke University from the National Cancer Institute, NIH, USPHS; by a grant from the American Cancer Society, Inc. (E-84A); and by the Dorothy Beard Research Fund.

Received 2/ 7/66.