Multicellular tumor spheroids of HeLa cells have been grown in a static culture system. Samples of spheroids were exposed for 2 h to graded concentration of cis-platinum and its analogue, carboplatin, and then response assayed by survival of clonogenic cells. The purpose of present experiment is to clarify the effectiveness of these platinum compounds and to evaluate intrinsic radiosensitivity of cells using spheroids of HeLa cells as an experimental in vitro model. Variations of the drug sensitivity of monolayers as well as spheroids were also evaluated in cell-survival curves. In cis-platinum concentration-survival curve, there was a large shoulder extending as far as $Cq=3.4{\mu}M$, after which there was exponential decrease in survival curve having a Co Value of $1.2{\mu}M$ in spheroids. While the Co for the spheroids was essentially no significant change, but Cq value was larger than that of monolayers. This suggest that the effect of cis-platinum is greater En the monolayer with actively proliferaing cells than hypoxic one. In the carboplatin concentration-survival curves, the Co value of spheroids was $15.0{\mu}M$ and the ratio with the Co from monolayer cell $(32.5{\mu}M)$ was 0.40, thus indicating that the spheroids had a greater sensitivity to carboplatin than monolayers. Therefore, the effect of carboplatin is mainly on the deeper layers of spheroids acting as hypoxic cell sensitizer. The enhanced effect was obtained for monolayer cells using combined X-ray and carboplatin treatment 2 hours before irradiation. The result shown in isobologram analysis for the level of surviving fraction at 0.01 indicated that the effect of two agents was trusty supra-additive. From this experimental data, carboplatin has excited much recent interest as one of the most promising, since it is almost without nephrotoxicity and causes less gastrointestinal toxicity than cis-platinum. Interaction between carboplatin and radiation might play an important role for more effective local tumor control.
In this study, two essential oils (EOs) extracted from Aleriana fauriei and Alpinia galangal were formulated as an emulsifiable concentrate (EC) and a granule. In the evaluation of their acute toxicity on fishes, Cyprinus carpio adults were used and the toxicities were determined in a static condition. The formulations were prepared from the essential oil extracted by three different methods namely steam distillation (SD), solvent extraction (SE) and supercritical fluid extraction (SFE). The acute toxicities were calculated using $LC_{50}$ values. Among EOs, only the EO extracted by solvent showed acute toxicities on carps. Some of the EC, EOs of Aleriana fauriei did not exhibit toxicity, while EOs from Alpinia galangal showed potent acute toxicities on carps. Among the granules, granules formulated with Aleriana fauriei EO extracted by SD method and Alpinia galangal EO extracted by SFE method showed acute toxicities on fishes. Nevertheless, $LC_{50}$ of ECs and granules formulated with all types of EOs in this study was higher than the fish toxicity level III for pesticides suggested by Korea Rural Development Administration. Furthermore, cytochrome P450 1A and glutathione S-transferase were confirmed as biomarkers in carps in response to the exposure to Alpinia galangal EO extracted by SD and SFE method, tracking Alpinia galangal EO in the aquatic environment.
The susceptibility of Aphis gossypii populations collected from three fields (WJ, CC, and GS) was evaluated to three insecticides (afidopyropen, chlorfenapyr and cyantraniliprole) and three binary mixtures. Three field populations showed resistance ratios of over 100 to all insecticides. The Combination Index (CI), %M(synergism), Co-Toxicity Coefficient (CTC), Wadley Ratio (WR), Synergism Ratio (SR) and Abbott Ratio (AR) were used to evaluate combined effect of the insecticides. Afidopyropen + chlorfenapyr (CI ≤ 0.16; %M(synergism) ≥ 94; CTC ≥ 764.5; WR ≥ 6.4; SR ≥ 6.9 and AR ≥ 1.1) showed a synergism in all filed populations. WJ and CC populations showed a synergism in all binary mixtures of insecticides, but GS population showed an antagonism for chlorfenapyr + cyantraniliprole (CI, 1.63; %M(synergism), 30; CTC, 64.0; WR, 0.6 and AR, 0.54) and afidopyropen + cyantraniliprole (CI, 6.7; %M(synergism), 1; CTC, 19.8; WR, 0.2 and AR ≤ 0.55). All mixtures (afidopyropen + chlorfenapyr, chlorfenapyr + cyantraniliprole and afidopyropen + cyantraniliprole) showed a control value of over 99% after 21 days of treatment in the field. This study highlights that binary mixtures of three insecticides serve as an effective control strategy for A. gossypii.
Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.
This study was conducted to discover new phytotoxins which may be used as lead molecules for the development of new herbicides. A total of 187 endophytic fungi were isolated from 11 plant species, which were collected from 8 locations in Korea. Their herbicidal activities were screened in vivo by herbicidal and duckweed bioassays after they were cultured in potato dextrose broth and rice solid media. Both fermentation broth and solid culture extract of Gliocladium catenulatum F0006 isolated from red pine (Pinus densiflora) showed 70% herbicidal activity only against cocklebur (Xanthium strumarium) out of the 10 weeds tested. Solid culture extract of F0034 isolated from arrowroot (Pueraria thunbergiana) exhibited 20 to 100% herbicidal activities against all of the weeds. Especially, shattercane (Sorghum bicolor), barnyardgrass (Echinochloa crus-galli), large crabgrass (Digitaria sanguinalis), and fall pauicum (Panicum dichtomiflorum) were sensitive to the solid culture extract of F0034. In addition, solid culture extract of F0043 isolated from red pine displayed 20% to 70% herbicidal activities only against 5 grass species, but not against 5 broad-leaf plant species. On the other hand, as the results of duckweed assay, 8 fermentation broths showed 100% growth inhibitory activity at concentrations less than 5.0% of culture supernatants and 12 solid cultures had a potent inhibitory activity against duckweed growth. A toxic metabolite was purified from the solid cultures of G. catenulatum F0006 by repeated column chromatography and bioassay. It caused a phytotoxic syndrome only on cocklebur out of the 10 weeds tested; it completely killed cocklebur seedlings at $500\;{\mu}g/ml$ and showed 85% herbicidal activity against cocklebur at $100\;{\mu}g/ml$. The molecular weight of the toxic metabolite is 238 daltons and its structure determination is underway.
Park, Na-Hye;Lee, Hwa-Yong;Choi, Jong-Woon;Park, Seung-Chun
The Korean Journal of Mycology
/
v.46
no.3
/
pp.295-306
/
2018
In the present study, we compared the effects of 50% ethanolic extracts of Chinese and Korean Wolfiporia cocos (CPE and KPE) on in vitro lipid accumulation in 3T3-L1 cells and their anticancer activities in Sarcoma 180 cells. We further compared the anticancer activities and the 50% inhibitory concentrations ($IC_{50}$) of CPE with KPE with cultivated for one and two years in a landfill and a facility (LPE and FPE), respectively. In addition, the single oral dose toxicities of CPE and KPE were evaluated in mice. Lipid accumulation was inhibited after 48 hours, in CPE and KPE treated 3T3-L1 cells; however, no significant difference was observed between CPE and KPE in their lipid accumulation inhibitory activities. The anticancer activity of KPE was higher than that of CPE at $300{\mu}g/mL$ (p<0.05), revealing the possibility of an auxiliary biological means for origin identification. The anticancer activities of LPE and FPE were significantly stronger than that of CPE (p<0.05) but there was no difference between extracts from one- and two-year-old W. cocos, irrespective of the cultivation method. In single oral dose toxicity tests, CPE and KPE did not induce mortality during the 14-day observation. Thus, the 50% of lethal dose ($LD_{50}$) of CPE and KPE were estimated to be higher than 2,000 mg/kg. Taken together, our results indicate that the anticancer assay could be an auxiliary means of identifying the origin of W. cocos. In addition, artificial cultivation could be an alternative way to reduce the import of W. cocos. Lastly, 50% ethanolic W. cocos extracts could be potential candidates for obesity and cancer managements.
A numerical variation and abnormalities were studied on egg bags and embryos of Korean salamander, Hynobius leechii from agricultural habitat. The teratogenic and toxic effects of fungicide benomyl were also investigated with early embryos from non-agricultural habitat. We collected 144 egg bags from agricultural region, and 3418 of early embryos were contained. The lengths of egg bags were varied from 10 to 23 cm and the most frequent length was 19 cm. The number of embryos was varied from 7 to 43, and the most frequent range was 22 to 26. Spontaneous abnormalities were occurred in 406 embryos among 116 egg bags, and 24 kinds of external abnormalities were found. Individuals showing severe external defect were histologically studied and they showed optic dyspalsia, thyroid carcinoma, somatic muscular dysplasia, partial biaxial structure, decrease of red blood cells in the heart, cephalic degeneration and intestinal dysplasia. 385 embryos from non-agricultural region were exposed to 200 nM${\sim}$ 1 ${\mu}$M of benomyl at blastula or gastrula for 12 days. All embryo were dead in the concentration of 1 ${\mu}$M (LD$_{100}$) and 75% of embryos were dead in 800nM of benomyl. Speciflc effect due to benomyl was acrania or cephalic dysplasia and this restult suggests that the benomyl inhibit stongly to the development of neural tissue. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of the movement of neural crest cells.
The flag and lower leaves (4th or 5th) of rice plant from the field of NPK simple trial and from three low productive area were analyzed in order to find out certain diagnostic criteria of nutritional status at harvest. 1. Nutrient contents in the leaves from no fertilizer, minus nutrient and fertilizer plots revealed each criterion for induced deficiency (severe deficient case induced by other nutrients), deficiency (below the critical concentration), insufficiency (hidden hunger region), sufficiency (luxuary consumption stage) and excess (harmful or toxic level). 2. Nitrogen contents for the above five status was less than 1.0%, 1.0 to 1.2, 1.2 to 1.6, 1.6 to 1.9 and greater than 1.9, respectively. 3. It was less than 0.3%, 0.3 to 0.4, 0.4 to 0.55 and greater than 0.55 for phosphorus $(P_2O_5)$ but excess level was not clear. 4. It was below 0.5%, 0.5 to 0.9, 0.9 to 1.2, 1.2 to 1.4 and above 1.4 for potassium. 5. It was below 4%, 4 to 6, 6 to 11 and above 11 for silicate $(SiO_2)$ and no excess was appeared. 6. Potassium in flag leaf seemed to crow out nitrogen to ear resulting better growth of ear by the inhibition of overgrowth of flag leaf. 7. Phosphorus accelerated the transport of Mg, Si, Mn and K in this order from lower leaf to flag, and retarded that of Ca and N in this order at flowering while potassium accelerated in the order of Mn, and Ca, and retarded in the order of Mg, Si, P and N at milky stage. 8. Transport acceleration index (TAI) expressed as (F_2L_1-F_1L_2)\;100/F_1L_1$ where F and L stand for other nutrient cotents in flag and lower leaf and subscripts indicate the rate of a nutrient applied, appears to be suitable for the effect of the nutrient on the translocation of others. 9. The content of silicate $(SiO_2)$ in the flag was lower than that of lower leaf in the early season cultivation indicating hinderance in translocation or absorption. It was reverse in the normal season cultivation. 10. The infection rate of Helminthosporium frequently occurred in the potassium deficient field seemed to be related more to silicate and nitrogen content than potassium in the flag leaf. 11. Deficiency of a nutrient occured simultaniously with deficiency of a few other ones. 12. Nutritional disorder under the field condition seems mainly to be attributed to macronutrients and the role of micronutrient appears to be none or secondary.
Kim, Dongwoo;Lee, Seungchel;Kim, Minjeong;Lee, Eunji;Yoo, ChangKyoo
Korean Chemical Engineering Research
/
v.54
no.5
/
pp.621-629
/
2016
Recently, the researches on quantitative structure activity relationship (QSAR) for describing toxicities or activities of chemicals based on chemical structural characteristics have been widely carried out in order to estimate the toxicity of chemicals in multiuse facilities. Because the toxicity of chemicals are explained by various kinds of molecular descriptors, an important step for QSAR model development is how to select significant molecular descriptors. This research proposes a statistical selection of significant molecular descriptors and a new QSAR model based on partial least square (PLS). The proposed QSAR model is applied to estimate the logarithm of partition coefficients (log P) of 130 polychlorinated biphenyls (PCBs) and lethal concentration ($LC_{50}$) of 14 PCBs, where the prediction accuracies of the proposed QSAR model are compared to a conventional QSAR model provided by OECD QSAR toolbox. For the selection of significant molecular descriptors that have high correlation with molecular descriptors and activity information of the chemicals of interest, correlation coefficient (r) and variable importance of projection (VIP) are applied and then PLS model of the selected molecular descriptors and activity information is used to predict toxicities and activity information of chemicals. In the prediction results of coefficient of regression ($R^2$) and prediction residual error sum of square (PRESS), the proposed QSAR model showed improved prediction performances of log P and $LC_{50}$ by 26% and 91% than the conventional QSAR model, respectively. The proposed QSAR method based on computational toxicology can improve the prediction performance of the toxicities and the activity information of chemicals, which can contribute to the health and environmental risk assessment of toxic chemicals.
Seo, Sam-Yeol;Srikanth, Koigoora;Kwon, Gi-Myon;Jang, Sin-Ae;Kim, Yong-Gyun
Korean journal of applied entomology
/
v.51
no.1
/
pp.47-58
/
2012
Effect of a new crop protectant 'Bt-Plus' on natural enemies was analyzed in this study. Tested natural enemies included two parasitic species of $Aphidius$$colemani$ and $Eretmocerus$$eremicus$, and four predatory species of $Harmonia$$axyridis$, $Orius$$laevigatus$, $Amblyseius$$swirskii$, and $Phytoseiulus$$persimilis$. 'Bt-Plus' was formulated by combination of three entomopathogenic bacteria ($Xenorhabdus$$nematophila$ (Xn), $Photorhabdus$$temperata$ subsp. $temperata$ (Ptt), $Bacillus$$thuringiensis$ (Bt)) and bacterial metabolite (BM). All three types of 'Bt-Plus' showed significantly higher toxicities against fourth instar $Plutella$$xylostella$ larvae than Bt single treatment. Two types of bacterial mixtures ('Xn+Bt' and 'Ptt+Bt') showed little toxicity to all natural enemies in both contact and oral feeding assays. However, 'BM+Bt' showed significant toxicities especially to two predatory mites of $A.$$swirskii$ and $P.$$persimilis$. The acaricidal effects of different bacterial metabolites were evaluated against two spotted spider mite, $Tetranychus$$urticae$. All six BM chemicals showed significant acaricidal effects. The BM mixture used to prepare 'Bt-Plus' showed a high acaricidal activity with a median lethal concentration at 218.7 ppm (95% confidence interval: 163.2 - 262.3). These toxic effects of bacterial metabolites were also proved by cytotoxicity test against Sf9 cells. Especially, benzylideneacetone, which was used as a main ingredient of 'BM+Bt', showed high cytotoxicity at its low micromolar concentration.
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