Alterations in bone marrow cell cycle kinetics by diphenylhydantoin and folate deficiency are restored by thymic...

We have previously shown that the anticonvulsant drug, diphenylhydantoin (DPH), causes impaired humoral immunity and host resistance in subchronically treated mice as a consequence of myelotoxicity. The bone marrow is a primary and sensitive target for this drug, which causes a selective loss of stem cells in S phase. The present report describes the restoration of stem cell kinetics by thymosin in both drug-treated and folate-deficient mice. Thymosin and the thymic peptide, FTS (facteur thymique serique), were also able to protect the progenitor stem cell, CFU-GM, from DPH inhibition in vitro, indicating a direct effect of both drug and thymic factors on stem cells. Although the mechanism of this protection is not yet understood, the observation may have important implications concerning immunotherapy of DPH-treated epileptics, who are at increased risk of infectious diseases and malignancies.