Benzimidazole pesticide carbendazim that is effective against a wide range of fungal plant pathogens is a protective, eradicant, and systemic fungicide. For genetic toxicity evaluation of carbendazim on DNA, genes and chromosome, were investigated with chromosome aberration, bacterial reverse mutation, micronucleus test in mouse born marrow and DNA damage assay by single cell microgel electrophoresis. Substitution and frameshift mutation were not induce at variable concentration of carbendazim on Ames test with or without rat liver microsomal activation. For the result of chromosome aberration test, numerical changes of chromosome were detected at the concentrations higher than $4.0{\mu}g/m{\ell}$, but structural aberration was not induced. Positive control, Mitomycin-C and captafol made a structural aberration, but numerical change of chromosome did not appear. In the micronucleus test for mouse born marrow, carbendazim was negative, but was weak positive in DNA damage assay by single cell microgel electrophoresis because of increased DNA moving length of 20% to control.
The suppressing effects of crude extracts of three Korean teas, persimmon leaf tea extract (PLTE), green tea extract (GTE) and oolong tea extract (OTE), were studied on the induction of sister chromatid exchange (SCE) in cultured Chinese hamster ovary cells. When cells were treated with tea extract after mitomycin C (MMC) treatment, the frequency of MMC-induced SCEs were decreased at the high concentration $(1000\;{\mu}g/mL)$ of PLTE in the presence of S9 mix and at low concentrations $(20{\sim}80\;{\mu}g/mL)$ of PLTE in the absence of S9 mix, Whereas GTE and OTE showed suppressing effects on the MMC-induced SCEs at low concentrations $(10{\sim}20\;{\mu}g/mL)$ for OTE and $160\;{\mu}g/mL$ for GTE only in the presence of S9 mix. MMC-induced SCEs were decreased by post-treatment with each tea extracts with S9 mix in the G1 phase of the cell cycle. These results suggest that PLTE, GTE and OTE could have bio antimutagenic activities, and also suggest that PLTE might have unknown antimutagenic components which would be responsible for the inhibitory effect against direct acting mutagenicity.
In this study, aniline dioxygenase genes responsible for initial catabolism of aniline in Burkholderia sp. HY1 and Delftia sp. HY99 were cloned and the amino acid sequences were comparatively analyzed, which already have been reported as bacteria utilizing aniline as a sole source of carbon and nitrogen, B. sp. HY1 was found to have at least a plasmid, and the plasmld-cured strain, B. sp. HY1-PC obtained using mitomycin C was tested with wild type strain to investigate whether the former maintained the degradability for aniline. This proved that the aniline oxygenase gene from B. sp. HY1 was located in chromosomal DNA, not in plasmid DNA. Aniline dioxygenase small subunits from B. sp. HY1 and D. sp. HY99 were found, based on 146 amino acids, to share 79% similarity. Notably, ado2 genes from B. sp. HY1 and D. sp. HY99 which were found to be terminal dioxygenase of aniline dioxygenase small subunit showed 99% similarity in the deduced amino acid sequences with tdnA2 of Frateuria sp. ANA-18 and danA2 of D. sp. AN3, respectively. Besides, enzyme assay and amino acid sequence analysis of catechol dioxygenase supported the previous report that B. sp. HY1 might occupy ortho-cleavage pathway using catechol 1,2-dioxygenase, while D. sp. HY99 might occupy catechol 2,3-dioxygenase for meta-cleavage pathway.
Kim, Chung-Hee;Kim, Jong-Soo;Van Cuong, Dang;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
Journal of Life Science
/
v.13
no.3
/
pp.241-247
/
2003
While the DNA-protein kinase (DNA-PK) complex, comprised of DNA-PKcs and Ku80, is primary involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type (Wt) or DNA-PKcs-null (DNA-$PKcs^{-/-}$) mice with various stress inducing agents revealed that adriamycin was markedly more cytotoxic for $Ku80^{-/-}MEFs$ and led to their long-term accumulation in the $G_2$/M phase. This differential response was not due to differences in DNA repair, since adrimycin-triggered DNA damage was repaired with comparable efficiency in both Wt and $Ku80^{-/-}MEFs$, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and $G_2$/M-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.
Purpose: The purpose of this study was to explore the dosimetric difference between simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and three-dimensional conformal radiotherapy (3DCRT), and the clinical outcomes of anal squamous cell carcinoma (ASCC) chemoradiotherapy featuring SIB-IMRT. Materials and Methods: This study included ten patients with ASCC who underwent chemoradiotherapy using SIB-IMRT with 5-fluorouracil and mitomycin C. SIB-IMRT delivered 54 Gy to each primary tumor plus metastatic lymph nodes and 45 Gy to regional lymph nodes, in 30 fractions. Four patients received additional boosts to the primary tumors and metastatic lymph nodes; the median total dose was 54 Gy (range, 54 to 60 Gy). We additionally created 3DCRT plans following the Radiation Therapy Oncology Group 9811 protocol to allow dosimetric comparisons with SIB-IMRT. Locoregional control, overall survival, and toxicity were calculated for the clinical outcome evaluation. Results: Compared to 3DCRT, SIB-IMRT significantly reduced doses to the external genitalia, bladder, and intestine, delivering the doses to target and elective nodal region. At a median follow-up time of 46 months, 3-year locoregional control and overall survival rates were 88.9% and 100%, respectively. Acute toxicities were treated conservatively. All patients completed radiotherapy with brief interruptions (range, 0 to 2 days). No patient experienced ${\geq}grade$ 3 late toxicity during the follow-up period. Conclusion: The dosimetric advantages of SIB-IMRT appeared to reduce the toxicity of chemoradiotherapy for ASCC achieving high locoregional control in the extended period.
Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients($95{\%}$) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus. and concurrent esophageal irradiation to 30 Gy. After that patients received 5-FU continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000mg/$m^2$ administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100mg/$m^2$ bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrentm chemoradiation twenty-six patients underwent radical esophagectomy. Results : Ninety-three patients could be examined for response assessment, By treatment modality, response rates were $85.1{\%}$ for radiation alone group and $86.3{\%}$ for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was $61.9{\%}$. The pathologic complete response were $15.4{\%}$ in operation group. Overall median survival was II months and actuarial 5-year survival rate was $8{\%}$. The median survival interval was 6 months for radiation alone group, 11 months for combined chemoradiation group and 19 months for operation group. And also median survival was 19 months for complete responder group that 8 months for noncomplete responder group. In univariative analysis, statistically significant prognostic factors were tumor size, clinical stage, tumor response, and operation. In multivariative analysis, significantly better survival was associated with clinical stage, tumor response, radiation dose, and operation. Conclusion : Compared with radiotherapy alone, combined multimodality may improve the median survival in patients with localized carcinoma of the esophagus and toxicity is acceptable.
BACKGROUND: in vitro micronucleus test (vitMNT) is one of the promising alternative testing methods in genotoxicity test and was adopted as OECD test guideline for chemical registration. This study was conducted to optimize the cytoplasm conditions in vitMNT using Chinese hamster lung (CHL) cell. METHODS AND RESULTS: In this study cytokinesis-block micronucleus test was conducted. Mitomycin C and colchicine were used as positive control chemicals and were treated for three hours (short time) or twenty-four hours (long time). Giemsa solution was used for cell staining. For optimization of vitMNT, the final fixative was prepared as five concentrations (0%, 1%, 3%, 5%, and 25%) of acetic acid in methanol, and treatment times of the final fixative were varied under four conditions (immediately, one hour, four hours, and one day). CONCLUSION: Acetic acid at 1% in methanol as the final fixative was most adequate to preserve the cytoplasm around the nucleus in the interphase cells. Also, fixative treatment time of cell suspension for one to four hours may minimize the cell rupture. These results can be helpful for getting an accurate result promptly due to clear visual distinction to score micronucleus in vitMNT using giemsa solution.
Purpose : Since February 1991 a Prospective study for non-small cell lung cancer patients who underwent radical resection and had a risk factor of positive resection margin or regional lymph node metastasis has been conducted to evaluate the effect of MVP chemotherapy and radiotherapy on the pattern of failure, disease free and overall survival. and tolerance of combined treatment. Materials and Methods: Twenty nine patients were registered to this study until Sep. 1993; of these 26 received planned therapy Within 3 weeks after radical resection, two cycles of MVP(Mitomycin C $6mg/m^2,$ Vinblastin $6mg/m^2,$ Cisplatin $60mg/m^2$) chemotherapy was given with 4 weeks intervals. Radiotherapy (5040cGy tumor bed dose and 900cGy boost to high risk area) was started 3 to 4 weeks after chemotherapy. Results: One and two year overall survival rates were $76.5\%\;and\;58.6\%$ respectively. Locoregional failure developed in 6 patients$(23.1\%)$ and distant failure in 9 patients$(34.6\%)$ Number of involved lymph nodes, resection margin positivity showed some correlation with failure pattern but T-stage and N-stage showed no statistical significance. The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70 days showed lower incidence of distant metastasis. Postoperative combined therapy were well tolerated without definite increase of complication rate, and compliance rate in this study was $90\%$. Conclusion: 1) MVP chemotherapy showed no effect on locoregional recurrence, but appeared to decrease the distant metastasis rate and 2) combined treatments were well tolerated in all patients. 3) The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70days showed lower incidence of distant metastasis. 4) Addition of chemotherapy to radiotherapy failed to increase the overall or disease free survival.
Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-${\alpha}$) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-${\alpha}$ (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP), and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE-IFN-${\alpha}$ group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-${\alpha}$ group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-${\alpha}$ combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. Conclusions: The use of the TACE and IFN-${\alpha}$ combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.
Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.
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