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Adriamycin-induced Delayed Erythropoietic Injury Expressed following Anemia Stress¹

Cancer Research Unit, Clinical Radiation Therapy Research Center, Division of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212

The present studies were undertaken to compare anemiainduced erythropoietic responses in femoral marrows and spleens of mice pretreated with Adriamycin (ADR) or 1-ß-D-arabinofuranosylcytosine with those of untreated age-matched controls. Mice were bled 45 or 120 days after drug treatment. The erythropoietic response to bleeding was quantitated by morphological, gravimetric, and radioiron methods 48 hr after bleeding. At 120 days after ADR, prebleeding base-line cellularity parameters were, in general, similar to those found in untreated age-matched controls. The response to the anemia stress was compared in drug-treated animals and in age-matched untreated controls, and the response deficit was expressed as residual injury (RI). At 120 days, ADR-induced RI was observed to be dose dependent in both femoral marrow and spleen. ADR-induced RI in femoral marrow and spleen were similar at 45 and 120 days, with no significant recovery. Although marrow RI was noted 45 days after 200 mg 1-ß-D-arabinofuranosylcytosine per kg, there was no RI at 120 days. The results indicate that ADR can induce a long-lasting hematopoietic injury which is not obvious from measures of homeostatic cellularity, but which can be expressed after induction of an acute proliferative demand.

¹ This investigation was supported by Grants CA-10438 and CA-20328 awarded by the National Cancer Institute, Department of Health, Education, and Welfare.

² To whom requests for reprints should be addressed, at Cancer Research Laboratories, Allegheny-Singer Research Corp., 320 East North Ave., Pittsburgh, Pa. 15212.

Received 10/ 5/79. Accepted 3/28/80.