PMID- 12020602 OWN - NLM STAT- MEDLINE DCOM- 20021114 LR - 20190916 IS - 0887-2333 (Print) IS - 0887-2333 (Linking) VI - 16 IP - 3 DP - 2002 Jun TI - Rat granulocyte colony-forming unit (CFU-G) assay for the assessment of drug-induced hematotoxicity. PG - 281-8 AB - To assess the drug-induced hematotoxicity to granulocyte progenitors, we established a modified colony-forming assay using rat bone marrow cells (BMCs). In the presence of various colony-stimulating factors (CSFs), rat BMCs were disseminated on methylcellulose at a concentration of 1.3 x 10(4) cells/cm(2) (5 x 10(4) cells/0.5 ml/well in a 12-well plate). Mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) stimulated the formation of almost all macrophage colonies. Human granulocyte colony-stimulating factor (hG-CSF) alone or in combination with mouse interleukin-3 (mIL-3) did not significantly effect on the number of rat colony-forming units in culture (CFU-C). When BMCs were seeded at 5.2 x 10(4) cells/cm(2) (5 x 10(5) cells/1 ml/dish in a 35-mm dish), hG-CSF increased the number of the colonies in a dose-dependent manner, and resulted in about 50 colonies at 50 ng/ml. The constituent cells of the colonies were identified as neutrophils. Under these conditions, the effects of 5-fluorouracil (5-FU) on granulocyte colony-forming units (CFU-G) were examined in rats and mice. The inhibitory effect of 5-FU on rat CFU-G was similar to the effect on mouse CFU-G. These results indicate that the rat CFU-G induced by hG-CSF is capable of being used for the evaluation of drug-induced hematotoxicity. FAU - Matsumura-Takeda, K AU - Matsumura-Takeda K AD - Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan. kuniko_m_t@research.otsuka.co.jp FAU - Kotosai, K AU - Kotosai K FAU - Ozaki, A AU - Ozaki A FAU - Hara, H AU - Hara H FAU - Yamashita, S AU - Yamashita S LA - eng PT - Journal Article PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Drug Combinations) RN - 0 (Hemolysin Proteins) RN - 0 (Interleukin-3) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - U3P01618RT (Fluorouracil) SB - IM MH - Animals MH - Bone Marrow Cells/*drug effects/pathology MH - Cells, Cultured MH - Colony-Forming Units Assay/*methods MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Fluorouracil/toxicity MH - Granulocyte Colony-Stimulating Factor/pharmacology MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Hemolysin Proteins/*toxicity MH - Humans MH - Interleukin-3/pharmacology MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Stem Cells/*drug effects/pathology MH - Toxicity Tests/*methods EDAT- 2002/05/22 10:00 MHDA- 2002/11/26 04:00 CRDT- 2002/05/22 10:00 PHST- 2002/05/22 10:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/05/22 10:00 [entrez] AID - S0278691502000480 [pii] AID - 10.1016/s0278-6915(02)00048-0 [doi] PST - ppublish SO - Toxicol In Vitro. 2002 Jun;16(3):281-8. doi: 10.1016/s0278-6915(02)00048-0.