No abstract

Chloramphenicol can inhibit protein synthesis in mammalian cell-free systems as effectively as it inhibits protein synthesis in analogous microbial systems. Significant inhibition in mammalian systems was obtained only when protein synthesis was stimulated by the addition of template RNA to the system, there being comparatively little inhibition of protein synthesis by ribosomes in the absence of stimulatory RNA. It is postulated that chloramphenicol may inhibit the function of messenger or template RNA by successfully competing for ribosomal binding sites, thereby preventing the attachment of RNA to ribosomes. The apparent discrepancy in the sensitivity of mammalian and microbial cells to chloramphenicol may be related to differences in turnover or stability of ribosomal template RNA rather than to intrinsic differences in mechanism of protein synthesis. These observations are in accord with the suggestion that protein synthesis in intact mammalian cells may be susceptible to chloramphenicol inhibition only at the time that new messenger or template RNA is being deposited on ribosomes and that more mature cells may be resistant because informative RNA already deposited on ribosomes is not accessible to chloramphenicol inhibition. The inhibitory effect of chloramphenicol on protein synthesis in proliferating cells may be an important factor in hematologic toxicity attributable to chloramphenicol.

Chloramphenicol is known to inhibit microbial protein synthesis both in intact cellsl-4 and in cell-free systems.5' 6 Similar inhibition of protein synthesis has not, however, been demonstrable in analogous mammalian systems.7-9 Matthaei and Nirenberg observed inhibition of protein synthesis by E. coli ribosomes with 0.3

A 26-year-old patient with acute lymphatic leukemic conceived while on systemic chemotherapy. This patient experienced relapse during the second trimester, and a second complete hematologic remission was achieved with doxorubicin hydrochloride, vincristine, and prednisone. A 2400-gram, but otherwise normal, male infant was delivered by Caesarean section during the 36th gestational week. Growth and development of this child is normal at six months.

Two patients with aplastic anemia evolving from cellular bone marrows with severely diminished megakaryocytes are reported. During this evolution a plasma inhibitor of in vitro granulocyte-macrophage colony formation was demonstrated associated with non-A, non-B hepatitis in one patient. The second patient had abnormal liver function that corrected after the delivery of a normal newborn but there was persistence of pancytopenia without evidence of a plasma inhibitor.