PMID: 9548417Apr 21, 1998Paper

Circadian-based effects of AcSDKP, with or without rhG-CSF on hematologic toxicity of chemotherapy in mice

European Journal of Haematology
X M LiF Lévi

Abstract

The hematologic toxicity of arabinosylcytosine (Ara-C) and carboplatin (CBDCA) as well as the stimulating effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on murine bone marrow vary according to their dosing time along the 24-h time scale. In the present study, we investigated whether the tolerability of Ara-C or CBDCA, given at their least toxic circadian time, could be improved further with AcSDKP, a negative regulator of hemopoiesis, rhG-CSF or both. A total of 228 B6D2F1 mice received once-daily injection of either Ara-C (42 mg/kg/d s.c.) for 7 d (d 0-6) at 8 hours after light onset - HALO) or CBDCA (40 mg/kg/d i.p.) for 5 d (d 2-6) at 16 HALO. AcSDKP (24 microg/d) was continuously infused for 7 d (d 0-6), using an osmotic minipump. rhG-CSF (400 microg/kg/d s.c.) was injected for 4 d (d 9-12) at 9 HALO. Subgroups of mice were sacrificed at 3 HALO on various days following treatment. AcSDKP significantly increased CFU-GM count on d 7 and leukocyte, neutrophil and monocyte counts on d 13 and d 16 compared to Ara-C alone. Also, rhG-CSF produced similar protective effects to those of AcSDKP with regard to leukocyte and CFU-GM counts. The combination of AcSDKP with rhG-CSF induced a further increase in...Continue Reading

References

Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M LenfantE Frindel
Nov 1, 1988·Toxicology and Applied Pharmacology·N A BoughattasA Reinberg
Jun 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·T Nakahata, M Ogawa
Nov 1, 1982·Zeitschrift Für Naturforschung. Section C: Biosciences·W R Paukovits, O D Laerum

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Citations

Jun 1, 2002·American Journal of Clinical Oncology·Shinya SatoNaoki Terakawa

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