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Suppression of Cellular Activity in the Reticuloendothelial System of the Rat by 7,12-Dimethylbenz(a)anthracene¹

Department of Medicine, University of Kentucky College of Medicine, Lexington, Kentucky 40506

A single feeding of 7,12-dimethylbenz(a)anthracene (DMBA) (112 or 133 mg/kg) to female Sprague-Dawley rats, age 50 days, induced maturation arrest at the proerythroblast, promyeloblast, and promegakaryocytoblast level in bone marrow, depletion of thymic lymphocytes, and disorganization of the lymphoid follicles in the spleen. The peripheral blood reflected these changes. A decrease in lymphocytes was first observed on Day 2 after DMBA. At this time the total granulocyte count was increased. Lymphocytopenia and granulocytopenia were maximal on Days 5 and 6, but granulocytopenia was more profound. Thrombocytopenia and its attendant hemorrhagic phenomena were maximal between Days 9 and 15. Morphologic changes indicative of damage were first apparent in marrow on Day 3 and of recovery from damage on Day 9; regenerative changes occurred rapidly after Day 15 and were virtually complete by Day 25. There was no evidence for direct damage to the formed elements in peripheral blood by this hydrocarbon. These changes closely mimic those induced by radiation and are probably the consequence of damage to DNA of the proerythroblast, myeloblast, and megakaryoblast precursors.

¹ This investigation was supported by USPHS Research Grant No-CA-07321.

² Present address: Medical Department, The Norwich Pharmacal Company, P.O. Box 191, Norwich, New York.

With the technical assistance of Dona Dunne, Thomas Roach, and Yvonne Spencer

Received 1/11/67. Accepted 10/15/67.