title: Biological time and the effects of hydroxyurea on DNA synthetic activity of bone marrow and tumor cells in mice bearing the Ehrlich ascites carcinoma.
abstract: The objective of this experiment was to attempt to induce, with hydroxyurea (HU), significant quantitative differences in the level of DNA-synthetic activity (DNA-SA) between a neoplastic cell population (the Ehrlich ascites carcinoma or EAC) and bone marrow in the same animal. Mice bearing a 5-day-old EAC were standardized to and kept on an LD 12:12 cycle (light 0600-1800 hr). They were treated with 500 mg/kg HU at 0500 hr (23 hr after lights on, or HALO) or at 1700 hr (11 HALO). DNA-SA was determined by liquid scintillation counting of 3H-thymidine incorporation into chemically isolated DNA. DNA-SA in bone marrow and EAC cells was monitored over the next 60 hr with subgroups of ten mice each killed every 3 hr beginning 3 hr after treatment with HU. The circadian system of the host influenced the response of the bone marrow to HU; i.e., the response to HU administered at 0500 hr was different both qualitatively and quantitatively from that for HU given at 1700 hr. Comparisons of DNA-SA in bone marrow and EAC from the same animal revealed time points after treatment with HU when DNA-SA in the EAC was high, but DNA-SA in bone marrow was low. These differences in the level of DNA-SA between a tumor cell population and bone marrow should be of therapeutic value; i.e., executor doses of anti-DNA-SA drugs such as cytosine arabinoside could be given at that point in time after treatment with HU when DNA-SA in the tumor was high, but DNA-SA in the bone marrow was low.
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000503:physiopathology*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects; D002940:Circadian Rhythm; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004334:Drug Administration Schedule; D006918:Hydroxyurea / Q000008:administration & dosage*; D051379:Mice
chemical_list: D004273:DNA, Neoplasm; D004247:DNA; D006918:Hydroxyurea