• The Korean Journal of Nuclear Medicine
• /
• v.32 no.6
• /
• pp.525-533
• /
• 1998

Purpose: Radiation adaptive response in human peripheral lymphocytes and mouse bone marrow cells was investigated using both metaphase analysis and micronucleus assay. We assessed the correlation between both tests. Materials and Methods: Two groups of the human peripheral lymphocytes and mouse bone marrow cells were exposed to low dose (conditioning dose, 0,18 Gy) or high dose (challenging dose, 2 Gy) ${\gamma}$-rays. The other 4 groups were exposed to low dose followed by high dose after several time intervals (4, 7, 12, and 24 hours, respectively). The frequencies of chromosomal aberrations in metaphase analysis and micronuclei in micronucleus assay were counted. Results: Chromosomal aberrations and micronuclei of preexposed group were lower than those of the group only exposed to high dose radiation. Maximal reduction in frequencies of chromosomal aberrations were observed in the group to which challenging dose was given at 7 hour after a conditioning dose (p<0.001). Metaphase analysis and micronucleus assay revealed very good correlation in both human lymphocytes and mouse bone marrow cells (r=0.98, p<0.001 ; r=0.99, p=0.001, respectively). Conclusion: Radiation adaptive response could be induced by low dose irradiation in both human lymphocytes and mouse bone marrow cells. There was a significant correlation between metaphase analysis and micronucleus assay.

• Reproductive and Developmental Biology
• /
• v.35 no.1
• /
• pp.23-31
• /
• 2011

Two piglets and one juvenile pig were used to investigate closely what types of cells express green fluorescent protein (GFP) and if any, whether the GFP-tagged cells could be used for stem cell transplantation research as a middle-sized animal model in bone marrow cells of recloned GFP pigs. Bone marrow cells were recovered from the tibia, and further analyzed with various cell lineage markers to determine which cell lineage is concurrently expressing visible GFP in each individual animal. In the three animals, visible GFP were observed only in proportions of the plated cells immediately after collection, showing 41, 2 and 91% of bone marrow cells in clones #1, 2 and 3, respectively. The intensity of the visible GFP expression was variable even in an individual clone depending on cell sizes and types. The overall intensities of GFP expression were also different among the individual clones from very weak, weak to strong. Upon culture for 14 days in vitro (14DIV), some cell types showed intensive GFP expression throughout the cells; in particular, in cytoskeletons and the nucleus, on the other hand. Others are shown to be diffused GFP expression patterns only in the cytoplasm. Finally, characterization of stem cell lineage markers was carried out only in the clone #3 who showed intensive GFP expression. SSEA-1, SSEA-3, CD34, nestin and GFAP were expressed in proportions of the GFP expressing cells, but not all of them, suggesting that GFP expression occur in various cell lineages. These results indicate that targeted insertion of GFP gene should be pursued as in mouse approach to be useful for stem cell research. Furthermore, cell- or tissue-specific promoter should also be used if GFP pig is going to be meaningful for a model for stem cell transplantation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.3
• /
• pp.197-206
• /
• 2021

Carnosol is a phenolic diterpene phytochemical found in rosemary and sage with reported anti-microbial, anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. This study aimed to investigate the effect of carnosol on the lineage commitment of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) into osteoblasts and adipocytes. Interestingly, carnosol stimulated the early commitment of mBMSCs into osteoblasts in dose-dependent manner as demonstrated by increased levels of alkaline phosphatase activity and Alizarin red staining for matrix mineralization. On the other hand, carnosol significantly suppressed adipogenesis of mBMSCs and downregulated both early and late markers of adipogenesis. Carnosol showed to induce osteogenesis in a mechanism mediated by activating BMP signaling pathway and subsequently upregulating the expression of BMPs downstream osteogenic target genes. In this context, treatment of mBMSCs with LDN-193189, BMPR1 selective inhibitor showed to abolish the stimulatory effect of carnosol on BMP2-induced osteogenesis. In conclusion, our data identified carnosol as a novel osteoanabolic phytochemical that can promote the differentiation of mBMSCs into osteoblasts versus adipocytes by activating BMP-signaling.

• Journal of Radiation Protection and Research
• /
• v.22 no.1
• /
• pp.1-7
• /
• 1997

Radiation protection by post-irradiation injection of the ginseng extract in mice was studied. Male ICR mice, 7 weeks old, were orally injected with ginseng extrat(100mg/kg) for 10 days, and with physiologocal saline as the control. Immediately after final injection, mice were whole body irradiated with 5.08Gy(Cs-137 ${\gamma}$-ray, central dose rate : 654Gy/h) which induced Bone marrow death. At 24h after irradiation, micronucleus test and metaphase analysis in bone-marrow were carried, blood cell were counted and the survival rate were carried for 30 days after the irradiation. Stimulated recovery by the extract was observed in thrombocyte count, but that phenomenom was not showed in the erythrocyte and leucocyte counts. The 30-day survival ratio was 5% and 65% for the control and experimental group. Frequencies of micronuclei per 1000 polychromatic erythrocytes were 79.5${\pm}$1.5 in experimental group, 185.9${\pm}$35.8 in control. And Abnormal chromosomes per 50 metaphases were 112 in experimental group and 143 in control.

• YAKHAK HOEJI
• /
• v.51 no.4
• /
• pp.235-238
• /
• 2007

To determine the regulatory roles of phosphodiesterase (PDE) inhibitors on $PGE_2$-induced osteoclastogenesis, we investigated the effect of PDE inhibitors on osteoclast formation in the presence of $PGE_2$. Among PDE isozyme specific inhibitors, milrinone, a selective PDE3 inhibitor, and rolipram, a specific PDE4 inhibitor, increased $PGE_2$-induced osteoclast formation in cocultures of mouse bone marrow cells and osteoblasts. To verify that whether the PDE3 and PDE4 inhibitors act indirectly on osteoblasts, we measured the concentration of intracellular cAMP in osteoblasts. Treatment of milrinone or rolipram increased $PGE_2$-stimulated cAMP levels in osteoblasts. Furthermore, northern blot analysis revealed that the PDE3 and PDE4 inhibitors works synergistically with $PGE_2$ to increase the expression of TRANCE mRNA in osteoblasts. On the contrary, the PDE3 and PDE4 inhibitors did not augment the number of osteoclasts differentiated from bone marrow cells by $PGE_2$. In conclusion, the stimulation of $PGE_2$-induced osteoclast formation by the PDE3 and PDE4 inhibitors are attributable to their indirect effect on osteoblasts, not to their direct effect on bone marrow-derived osteoclast precursors.

• Environmental Mutagens and Carcinogens
• /
• v.24 no.1
• /
• pp.25-32
• /
• 2004

To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this resepct, the clastogenicity of 17 synthetic chemicals was evaluated with bone marrow micronucleus assay in mice. The positive control, mitomycin C (2 mg/kg, i.p.) revealed significant induction ratio of percentage of micronucleated polychromatic erythrocytes/1,000 polychromatic erythrocytes compared to solvent controls. The chemicals with relatively high $LD_{50}$ value such as allyl alcohol (CAS No. 107-18-6), 2,4-pentanedione (CAS No. 123-54-6) and 4-chloro-3,5-dimethylphenol (CAS No. 88-04-0) revealed no significant induction of micronucleated polychromatic erythrocytes in mice. From this results, 17 synthetic chemicals widely used in industry have revealed no significant micronucleus induction of clastogenicity in mice in this experiment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.3
• /
• pp.157-164
• /
• 2022

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

• YAKHAK HOEJI
• /
• v.37 no.3
• /
• pp.278-285
• /
• 1993

The anticlastogenic effect of N-acetylcysteine was tested in vivo in mouse bone-marrow micronucleus assay. The frequencies of micronuclei induced by adriamycin (5 mg/kg i.p.) in bonemarrow cells were decreased by the oral administration of N-acetylcysteine at 12 h before adriamycin injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of N-acetylcysteine. The anticlastogenic effects of SH compound including N-acetylcysteine, cysteine, cystine, S-carboxy methylcysteine and glutathione were also investigated by the multiple pretreatment. Each SH compound was administered orally every day for 5 days and adriamycin (5 mg/kg i.p.) was injected at 24h after the last dose of test compound. N-acetylcysteine and glutathione showed significantly the suppressive effect at dose of 10 and 25 mg/kg for N-acetylcysteine and at the dose of 25 mg/kg for glutathione. Our study suggests that N-acetylcysteine is capable of protecting the chromosomal damages in the normal cells during cancer chemotherapy by adriamycin, and may act as an anticlastogen against induction of micronuclei by superoxide generating agent such as adriamycin.

• Toxicological Research
• /
• v.5 no.2
• /
• pp.71-77
• /
• 1989

A mouse whole animal bioassay was employed to screen for potential mutagenicity of ethanol/water extracts of 16 Chinese herbal drugs that are commonly prescribed in Korea. Specific cytogenetic toxicity was measrured by recording evidence of clastogenesis toxicity was measured by recording evidence of clastogenesis via the mouse bone marrow micronucleus test. Male ICR mice administered ethanol extract of Pinelliae tuber (Pinellia eternata Breitenbach, ARACEAE, 양복) and ddY female mice administered extract of Angelica Koreanae radix(Angelica Koreana Maximowicz, UMBELLIFERAE, ) (both by oral administration, at a dose of 600 mg/kg), in a short-term dosing schedule, demonstrated significant increase in micronucleated polychromatophilic erythrocytes, indicating the increase of clastogenicity.

• Korean Journal of Acupuncture
• /
• v.36 no.1
• /
• pp.74-80
• /
• 2019

Objectives : TA, a polyherbal extract, typically is used for pharmacopuncture therapy on patients with traffic accident-related injuries and musculoskeletal diseases. This study was performed to evaluate the safety of the TA extract, using a micronucleus test. Methods : The dose range and sampling time were first established. An in vivo micronucleus test was then performed to determine the induction of micronuclei in mouse bone marrow cells after a single intramuscular administration of TA to 7-week-old ICR mice (0.2 ml/animal, at 24 hours post-dosing). Results : The incidence of micro-nucleated polychromatic erythrocytes (PCEs) in PCEs in the TA group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. The positive- and negative-control groups did not differ in the ratio of PCEs to total erythrocytes. Conclusions : Our toxicity study indicates that the TA extract does not induce micronucleus formation in mouse bone marrow cells.