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Pilot Study for the Prediction of Response to Radiotherapy Using [$^{18}F$]Fluorothymidine PET in Nasopharyngeal Cancer: Comparison with [$^{18}F$]FDG PET (비인두암에서 [$^{18}F$]Fluorothymidine PET을 이용한 방사선치료 반응도 예측을 위한 예비 연구: [$^{18}F$]FDG PET와의 비교)

  • Baek, So-Ra;Chae, Sun-Young;Kim, Hye-Ok;Lee, sang-Wook;Oh, Seung-Jun;Im, Ki-Chun;Moon, Dae-Hyuk;Kim, Jae-Seung;Ryu, Jin-Sook
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.6
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    • pp.535-542
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    • 2009
  • Purpose: This study was performed to know whether [$^{18}F$]Fluorothymidine (FLT) positron emission tomography (PET) can be used to monitor early response to radiotherapy in comparison with [$^{18}F$]Fluorodeoxyglucose (FDG) PET, and to establish the optimal imaging time for prediction of therapy response. Materials and Methods: Two patients with nasopharyngeal cancer underwent serial FLT PET and FDG PET before and during radiotherapy. Three on-treatment FLT and FDG PET scans were performed on 1 week, 2 weeks and 3 weeks (at each time of 10 Gy, 20 Gy and 30 Gy delivered). The peak standardized uptake values ($SUV_{peak}$) of primary tumors were measured on FLT and FDG PET. Then, percent changes of $SUV_{peak}$ after therapy were calculated. Results: In two patients, baseline values of $SUV_{peak}$ on FDT PET were higher than those on FLT PET (FLT vs FDG; 3.7 vs 5.0, and 5.7 vs 15.0). In patient 1, FLT $SUV_{peak}$ showed 78%, 78% and 84% of decrease on 1 week, 2 and 3 weeks after treatment, whereas FDG $SUV_{peak}$ showed 18%, 52% and 66% of decrease, respectively. In patient 2, FLT $SUV_{peak}$ showed 75%, 75% and 68% of decrease, whereas FDG $SUV_{peak}$ showed 51%, 49% and 58% of decrease, respectively. Both patients reached to complete remission after radiotherapy. Conclusion: After radiotherapy, the decrease of FLT tumor uptake preceded the decrease of FDG tumor uptake in patients with nasopharyngeal cancer, and 1 week after therapy may be appropriate time for the assessment of early response. FLT PET might be more useful than FDG PET for monitoring early response to radiotherapy.

The Anticancer Effect and Mechanism of Photodynamic Therapy Using 9-Hydroxypheophorbide-a and 660 nm Diode Laser on Human Squamous Carcinoma Cell Line. (9-hydroxypheophorbide-a와 660 nm 다이오드 레이저를 이용한 광역학치료의 항암효과와 치료기전에 대한 연구)

  • Ahn, Jin-Chul
    • Journal of Life Science
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    • v.19 no.6
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    • pp.770-780
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    • 2009
  • A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

Serial Ultrasonographic Appearance of Postpartum Uterine Involution in Cocker Spaniel Bitches (Cocker Spaniel 개에서 분만 후 자궁수복의 연속적 초음파상)

  • Hwang S. S.;Oh K. S.;Kim B. S.;Jo Y. T.;Park C. H.;Kim J. T.;Park I. C.;Park J. T.;Park S. G.;Son C. H.
    • Journal of Embryo Transfer
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    • v.20 no.3
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    • pp.271-277
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    • 2005
  • This study was undertaken to determine the normal appearance of the postpartum uterine involution. Postpartum changes in uterine shape, architecture, echogenicity and diameter were monitored with ultrasonography in 8 Cocker spaniel bitches. The excretory period of vaginal discharges in 8 normal bitches of uterine involution was finished completely at 23.20$\pm$2.77 days (Mean$\pm$SD) postpartum. The short axis shape of the uterus was varied from polygonal to circular. This lasted until 1600$\pm$2.12 days Postpartum, during which time the short axis uterine shape gradually changed to circular. Also, the long axis shape of the uterus was created a beaded appearance of the horns until 25.60$\pm$2.51 days postpartum. The uterine diameter was decreased not only in the placental sites from 24.20$\pm$2.06mm at 1 day to 13.18$\pm$0.84mm at 7 days postpartum, but also in the interplacental sites 14.26$\pm$2.22mm at 1 day, 9.81$\pm$0.7mm at 7 days postpartum. There was a general trend of decreasing uterine diameter, which occurred more rapidly at the placental sites. In conclusion, normal postpartum uterine involution in Cocker spainel bitches appeared to be completed around 68 days postpartum by gross findings such as vaginal discharges, and by ultrasongraphic findings, uterine shape and echogenicity.

Clinical Report of 46 Intracranial Tumors with LINAC Based Stereotactic Radiosurgery (선형가속기를 이용한 뇌종양 46예의 뇌정위다방향방사선치료 성적)

  • Yoon Sei C;Suh Tge S;Kim Sung W;Kang Ki M;Kim Yun S;Choi Byung O;Jang Hong S;Choi Kyo H;Kim Moon C;Shinn Kyung S
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.241-247
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    • 1993
  • Between July 1988 and December 1992, we treated 45 patients who had deep seated inoperable or residual and/or recurrent intracranial tumors using LINAC based stereotactic radiosurgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Treated intracranial tumors included pituitary tumors (n=15), acoustic neurinomas (n=8), meningiomas (n=7), gliomas (n=6), craniopharyngiomas (n=4), pinealomas (n=3), hemangioblastomas (n=2), and solitary metastatic tumor from lung cancer (n=1). The dimension of treatment field varied from 0.23 to 42.88 $cm^3\;(mean;\;7.26\;cm^3)$. The maximum tumor doses ranging from 5 to 35.5 Gy (mean; 29.9 Gy) were given, and depended on patients' age, target volume, location of lesion and previous history of irradiation. There were 22 male and 23 female patients. The age was varied from 5 to 74 years of age (a median age; 43 years). The mean duration of follow-up was 35 months (2~55 months). To date, 18 $(39.1\%)$ of 46 intracranial tumors treated with SRS showed absent or decrease of the tumor by serial follow-up CT and/or MRI and 16 $(34.8\%)$ were stationary, e.g. growth arrest. From the view point of the clinical aspects, 34 $(73.9\%)$ of 46 tumors were considered improved status, that is, alive with no evidence of active tumor and 8 $(17.4\%)$ of them were stable, alive with disease but no deterioration as compared with before SRS. Although there showed slight increase of the tumor in size according to follow-up imagings of 4 cases (pituitary tumor 1, acoustic neurinomas 2, pinealoma 1), they still represented clinically stable status. Clinically, two $(4.4\%)$ Patients who were anaplastic astrocytoma (n=1) and metastatic brain tumor (n=1) were worsened following SRS treatment. So far, no serious complications were found after treatment. The minor degree headache which could be relieved by steroid or analgesics and transient focal hair loss were observed in a few cases. There should be meticulous long term follow-up inall cases.

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Fractionated Stereotactic Radiation Therapy for Intracranial Benign Tumor : Preliminary Results of Clinical Application (양성 뇌종양의 분할정위 방사선치료 : 임상적 응용의 예비적 결과)

  • Kim Dae Yong;Ahn Yong Chan;Huh Seung Jae;Choi Dong Rak;Nam Jong Hyun;Lee Jung Il;Park Kwan;Nam Do-Hyun;Kim Moon Kyung
    • Radiation Oncology Journal
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    • v.16 no.2
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    • pp.185-194
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    • 1998
  • Purpose : With the development of stereotactic immobilization systems capable of reliable serial repositioning, fractionated stereotactic radiation therapy (FSRT) offers the Potential for an improved treatment outcome by excellent dose delivery, and dose distribution characteristics with the favorable radiobiological properties of fractionated irradiation. We describe our initial experience using FSRT for the treatment of intracranial benign tumor. Materials and Methods : Between August 1995 and December 1996. 15 patients(7 males and 8 females aged 6-70 years) were treated with FSRT. The patients had the following diagnosis pituitary adenoma(10) including one patient who previously had received radiotherapy, craniopharyngioma (2), acoustic neurinoma (1), meningioma (2). Using the Gill-Thomas-Cosman relocatable head frame and multiple non-coplanar therapy, the daily dose of 2Gy was irradiated at 90% to 100% isodose surface of the isocenter The collimator sizes ranged from 26mm to 70mm. Results : In all patients except one follow-up lost, disease was well-controlled. Acute complication was negligible and no patient experienced cranial nerve neuropathies and radiation necrosis. In overall patient setup with scalp measurements, reproducibility was found to have mean of $1.1{\pm}0.6mm$ from the baseline reading. Conclusion : Relocatable stereotactic system for FSRT is highly reproducible and comfortable. Although the follow-up period was relatively short. FSRT is considered to be a safe and effective radiation technique as the treatment of intracranial tumor. But the fractionation schedule(fraction size, overall treatment time and total dose) still remains to be solved by further clinical trials.

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Radiation-induced Pulmonary Toxicity following Adjuvant Radiotherapy for Breast Cancer (유방암 환자에서 보조적 방사선치료 후의 폐 손상)

  • Moon, Sung-Ho;Kim, Tae-Jung;Eom, Keun-Young;Kim, Jee-Hyun;Kim, Sung-Won;Kim, Jae-Sung;Kim, In-Ah
    • Radiation Oncology Journal
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    • v.25 no.2
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    • pp.109-117
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    • 2007
  • [ $\underline{Purpose}$ ]: To evaluate the incidences and potential predictive factors for symptomatic radiation pneumonitis (SRP) and radiographic pulmonary toxicity (RPT) following adjuvant radiotherapy (RT) for patients with breast cancer. A particular focus was made to correlate RPT with the dose volume histogram (DVH) parameters based on three-dimensional RT planning (3D-RTP) data. $\underline{Materials\;and\;Methods}$: From September 2003 through February 2006, 171 patients with breast cancer were treated with adjuvant RT following breast surgery. A radiation dose of 50.4 Gy was delivered with tangential photon fields on the whole breast or chest wall. A single anterior oblique photon field for supraclavicular (SCL) nodes was added if indicated. Serial follow-up chest radiographs were reviewed by a chest radiologist. Radiation Therapy Oncology Group (RTOG) toxicity criteria were used for grading SRP and a modified World Health Organization (WHO) grading system was used to evaluate RPT. The overall percentage of the ipsilateral lung volume that received ${\geq}15\;Gy\;(V_{15}),\;20\;Gy\;(V_{20})$, and $30\;Gy\;(V_{30})$ and the mean lung dose (MLD) were calculated. We divided the ipsilateral lung into two territories, and defined separate DVH parameters, i.e., $V_{15\;TNGT},\;V_{20\;TNGT},\;V_{30\;TNGT},\;MLD_{TNGT}$, and $V_{15\;SCL},\;V_{20\;SCL},\;V_{30SCL},\;MLD_{SCL}$ to assess the relationship between these parameters and RPT. $\underline{Results}$: Four patients (2.1%) developed SRP (three with grade 3 and one with grade 2, respectively). There was no significant association of SRP with clinical parameters such as, age, pre-existing lung disease, smoking, chemotherapy, hormonal therapy and regional RT. When 137 patients treated with 3D-RTP were evaluated, 13.9% developed RPT in the tangent (TNGT) territory and 49.2% of 59 patients with regional RT developed RPT in the SCL territory. Regional RT (p<0.001) and age (p=0.039) was significantly correlated with RPT. All DVH parameters except for $V_{15\;TNGT}$ showed a significant correlation with RPT (p<0.05). $MLD_{TNGT}$ was a better predictor for RPT for the TNGT territory than $V_{15\;SCL}$ for the SCL territory. $\underline{Conclusion}$: The incidence of SRP was acceptable with the RT technique that was used. Age and regional RT were significant factors to predict RPT. The DVH parameter was good predictor for RPT for the SCL territory while $MLD_{TNGT}$ was a better predictor for RPT for the TNGT territory.

The Usefulness of F-18 FDG PET to Discriminate between Malignant and benign Nodule in Idiopathic Pulmonary Fibrosis (특발성 폐섬유증에서 발견된 폐결절의 악성여부 감별에서 F-18 FDG PET의 유용성)

  • Kim, Bom-Sahn;Kang, Won-Jun;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.3
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    • pp.163-168
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    • 2006
  • Purpose: Incidence of lung canter in patients with idiopathic pulmonary fibrosis (IPF) is known to be higher than that in general population. However, it is difficult to discriminate pulmonary nodule in patients with IPF, because underlying IPF can be expressed as lung nodules. We evaluated the diagnostic performance of FDG PET in discriminating lung nodule in patients with IPF. Methods: We retrospectively reviewed 28 lung nodules in 16 subjects (age; $67.53{\pm}9.53$, M:F=14:2). Two patients had previous history of malignant cancer (small cell lung cancer and subglottic cancer). The diagnostic criteria on chest CT were size, morphology and serial changes of size. FDG PET was visually interpreted, and maximal SUV was calculated for quantitative analysis. Results: from 28 nodules, 18 nodules were interpreted as benign nodules, 10 nodules as malignant nodules by histopahthology or follow-up chest CT. The sensitivity and specificity of FDG PET were 100% and 94.4%, while those of CT were 70.0% and 44.4%, respectively. Malignant nodule was higher maxSUV than that of benign lung nodules ($7.68{\pm}3.96\;vs.\;1.22{\pm}0.65$, p<0.001). Inflammatory lesion in underlying IPF was significantly lower maxSUV than that of malignant nodules ($1.80{\pm}0.43$, p<0.001). The size of malignant and benign nodule were $23.95{\pm}10.15mm\;and\;10.83{\pm}5.23mm$ (p<0.01). Conclusion: FDG PET showed superior diagnostic performance to chest CT in differentiating lung nodules in patients with underlying IPF. FDG PET could be used to evaluate suspicious malignant lung nodule detected by chest in patients with IPF.

Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy (유방암 절제술 후 방사선치료를 시행한 환자의 골스캔에서 보이는 방사전 유발 늑골골절)

  • Kim, Hae-Won;Won, Kyoung-Sook;Zeon, Seok-Kil;Kim, Jin-Hee
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.4
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    • pp.287-293
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    • 2009
  • Purpose: This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Materials and Methods: Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest a findings of rib fracture were analyzed. Results: The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p = 0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p =0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest a, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p = 0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p = 0.001). Conclusion: Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis.

Immunohistochemical Study on the Superovulation Effected by Repeat of PMSG Administration in Rats 1. The Frequency of PMSG Administrations and Number of Follicles (PMSG 반복투여가 Rat의 과배란에 미치는 영향에 대한 면역조직화학적 연구 1. 투여회수에 따른 난포수의 차이)

  • 곽수동
    • Korean Journal of Animal Reproduction
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    • v.21 no.3
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    • pp.255-264
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    • 1997
  • The purpose of this study was attempted to investigate the number changes of the growing and mature follicles in ovary following repeats of pregnant mare serum gonadotropin(PMSG) treatments for superovulation in nulliparous rats. Thirty two rats(Sprague-Dawely, about 200~250 gm) were randomized into 4 groups. Control group rats were sacrified at estrus phase confirmed by vaginal smear. PMSG-treated group 1 rats, PMSG-treated group 2 rats and PMSG-treated group 3 rats were sacrified at 48 hrs after injection once with PMSG 25 IU, after 2 repeated injection by a week interval, and 3 repeated injection, respectively. The uteri and ovaries of rats were removed and weighed and then were observed grossly and serial sections of all ovaries and some sections of uteri by paraffin embedding were stained with H-E. Number of ovarian follicles about 3 grades of small, middle and large follicles from seondary and follicles were investigated by LM photographies of ovary preparations. The criteria of the small, middle, and large follicles were based as small follicle with preantral follicles with 2~4 layers of granulosa cells surrounding the oocyte, as secondary follicles with more than 5 layers of granulosa cells and early signs of antral cavity or with small clefts on either side of the oocytes, and as tirtiary follicles with a single medium sized antral cavity or large well-formed antral cavity, respectively. In gross findings, the wall of the uteri in control group were thin, and those in 3 PMS-treated group were markedly thickened and some uterine lumen of those filled with fluid. In histological findings, the walls of the uteri from 3 PMSG-treated groups were hypertrophied and their blood and lymph vessels were dilated than those of control group. The ovaries fo 3 PMSG-treated groups were more increased in size and the cortexes were more developed and increased in width but there are no difference of development and changes in 3 PMSG-treated groups. The weight of the uteri and ovaries per rat in PMSG -treated group 1, 2 and 3 were a, pp.ared to be significantly increased 171.4$\pm$47.6%, 162.3$\pm$43.9%, 206.9$\pm$30.4%, respectively than those of control groups. The mean number of follicle per ovary in control group were a, pp.ared to be 17.1$\pm$3.5, 46.2$\pm$14.5, and 74.3$\pm$22.7 at large, middle and small follicles, respectively and total number of these 3 grade follicles per ovary were a, pp.ared to be 137.7$\pm$31.7. The mean number of follicle per ovary in PMSG-treated group 1 were a, pp.ared to be 25.6$\pm$7.3, 78.1$\pm$29.9, and 83.2$\pm$34.0, at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 187.5$\pm$58.8. The mean number of follicle per ovary in PMS-treated group 2 were a, pp.ared to be 21.9$\pm$5.2, 67.8$\pm$16.8, and 68.0$\pm$14.9 at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 157.7$\pm$26.2. The mean number of follicle per ovary in PMS-treated group 3 were a, pp.ared to be 21.7$\pm$4.8, 61.5$\pm$17.0, and 59.7$\pm$16.2 at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 143.5$\pm$29.6. The number of follicles in PMSG-treated group 1 a, pp.ared to be more number than other 2 PMSG-treated gruops and tended to be decreased by frequency of PMSG-treatment.

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Toxic effects of phenanthrene on fertilization and normal embryogenesis rates of Mesocentrotus nudus and Hemicentrotus pulcherrimus (둥근성게(Mesocentrotus nudus)와 말똥성게(Hemicentrotus pulcherrimus)의 수정 및 정상 배아발생률을 이용한 Phenanthrene의 독성영향)

  • Choi, Hoon;Lee, Ju-Wook;Park, Yun-Ho;Lee, Seung-Min;Choi, Yoon-Seok;Heo, Seung;Hwang, Un-Ki
    • Korean Journal of Environmental Biology
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    • v.38 no.3
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    • pp.333-342
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    • 2020
  • The aim of this study was to define the toxic effects of phenanthrene (PAHs) on the fertilization and normal embryogenesis rates in the two species of sea urchin (Hemicentrotus pulcherrimus and Mesocentrotus nudus). The sperm and fertilized eggs of both sea urchin species were exposed to serial dilutions of phenanthrene for 10 min and 48 hours, respectively. The fertilization rate and normal embryogenesis rate of H. pulcherrimus and M. nudus were decreased in a concentration-dependent manner. The EC50 for the fertilization rate of H. pulcherrimus and M. nudus was 17.48 mg L-1 and 16.21 mg L-1, and the EC50 for the normal embryogenesis rate was 2.99 mg L-1 and 0.36 mg L-1, respectively. Between the two species, H. pulcherrimus was more sensitive to phenanthrene exposure, and 48 h normal embryogenesis was the more sensitive endpoint. Therefore, the results of this study demonstrated that the exposure of both sea urchin species to phenanthrene caused alterations in egg fertilization and the early developmental stages.