• 자연과학논문집
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• 제9권1호
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• pp.45-52
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• 1997

저농도의 MNNG가 Aspergillus nidulans의 생존도 및 돌연변이 유발에 끼치는 영향을 조사하였다. Nontoxic하고 submutagenic한 농도의 MNNG 선 처리는 높은 농도로 처리 시의 치사율 및 돌연변이 유발을 낮추지 못했다. 이러한 결과는 Aspergillus nidulans에는 MNNG 에 의한 adaptive response가 일어나지 않는다는 것을 시사하고 있다. 발아 과정의 첫 번째 체세포 분열에서, 시간별로 MNNG에 대한 치사율을 조사하고 UV에 의한 생존도와 비교하였다. UV나 MNNG 처리 시 치사율은 S 세포 시기 직전까지 증가하였다가, DNA 복제 시에는 감소함을 나타내었다. MNNG 처리 시는 UV와 달리 G2세포시기에 치사율이 가장 높았다.

• 대한의생명과학회지
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• 제7권4호
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• pp.205-210
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• 2001

Whereas apoptosis is a critical mode of cell deletion in normal organism development, apoptotic cells are also observed in tumor therapy. We therefore investigated the expression of apoptotic cells induced as a function of time and dose in murine A-20 lymphoma treated with cyclophosphamide in vivo, by H&E and TUNEL method. The percent of apoptotic cells were scored from tumor section using TUNEL method. The expression of apoptotic positive cell was determined over a 10-day period following treatment of the mice with 200 mg/kg. Apoptosis increased further with time, reaching a peak value between 12~24 hr (scored 6.7$\pm$1.0%~6.1$\pm$0.7%), and then slowly declined to background levels by 10 days after treatment. The dependence of induction of apoptosis on the dose of cyctophosphamide was determined by treatment with 50, 100, or 200 mg/kg at 12 hr after treatment. Apoptosis was dose dependent in that as the dose was increased the percentage of apoptosis increased. However, the increase in apoptosis at the lower dose used (50 mg/kg) was higher on a per unit dose basis than that at the higher dose used (200 mg/kg). This result show that the alkylating agent cyclophosphamide strongly induces apoptosis in murine lymphoma.

• BMB Reports
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• 제31권2호
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• pp.183-188
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• 1998

2-chloroethylethyl sulfide (CEES) is an alkylating agent that readily reacts with a wide variety of biological molecules causing metabolic abnormality. The mechanism of cell death during CEES injury is poorly understood. We have examined the effect of exposure of thymocytes with various concentrations of CEES to determine the pattern of cell death in thymocytes injury induced by CEES. In the present study, we show that two patterns of cell death occurred by either one of two mechanisms: apoptosis and necrosis. Exposure to low level of CEES (100 ${\mu}M$) for 5 h caused an induction of apoptosis on thymocytes, as identified by the following criteria: DNA fragmentation visualized by the characteristic "ladder" pattern was observed upon agarose gel electrophoresis and morphological features were revealed by microscopical observations. In contrast, exposure to high levels of CEES (500 ${\mu}M$) induce necrotic features such as cell lysis. Thus, depending on the concentrations, CEES can result in either apoptotic or necrotic cell damage. Our findings suggest that thymocytes which are not killed directly, but merely injured by low levels of CEES, are able to activate an internally-programmed cell death mechanism, whereas thymocytes receiving severe damages apparently can not.

• 생명과학회지
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• 제12권2호
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• pp.182-187
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• 2002

본 연구에서는 알킬화제인 methylmethane sulfonate (MMS)를 선처리한 NIH3T3세포에서 소목추출물의 효과를 분석하였다. MTT 분석결과 MMS에 의해서 유도된 세포생존률이 소목추출물에 의해서 감소되었다. 세포형태분석, acridine orange 염색법, 그리고 DNA fragmentation 분석에서 MMS에 의해서 유도된 세포고사의 특징인 핵 응축 및 DNA laddering이 소목추출물에 의해서 증가됨이 관찰되었다. 이러한 결과들로 소목추출물은 NIB73T3 세포에서 MMS에 의해서 유도된 세포고사를 촉진시킴을 보여준다.

• 대한기관식도과학회지
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• 제9권2호
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• pp.60-64
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• 2003

Restenosis frequently develops with granulation and overgrowth of scar following surgical treatment for laryngotracheal stenosis. Various methods such as stenting or CO2 laser application have been used to prevent restenosis, but they were seldom unsatisfactory. Mitomycin is an antineoplastic antibiotics derived from Streptomyces caespitosus; it inhibits fibroblast proliferation and acts as an alkylating agent to inhibit DNA synthesis. This study was desinged to evaluate effectiveness and determine indications of usage of topical mitomycin for laryngotracheal stenosis as a nonsurgical means of reducing postoperative granulation and scar tissue formation. Patients and Method : A retrospective study was performed on eight cases of laryngotracheal stenosis with topical mitomycin application. The author analyzed clinical outcomes of operative treatment with topical mitomycin. Patients underwent laryngotracheal reconstruction, endoscopic granulation removal, or bronchoscopic bougienage followed by topical application of mitomycin (0.4 mg/$m{\ell}$, 4minuntes) on the lesion intraoperatively. Result : Overall success rate of decannulation was 38% ($\frac{3}{8}$). Successful decannulation was possible in 75% ($\frac{3}{4}$) of laryngeal stenosis patients, 75% ($\frac{3}{4}$) of children, 60% ($\frac{3}{5}$) of the patients without previous surgery, and 75% ($\frac{3}{4}$) of bronchoscopic bougienage. Conclusion : The topical application of mitomycin in laryngotracheal stenosis was effective in untreated pediatric laryngeal stenosis which underwent bronchoscopic bougienage. Our results show that the topical mitomycin application for laryngotracheal stenosis could be a effective adjuvant treatment.

• Mycobiology
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• 제39권4호
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• pp.272-277
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• 2011

Chemical mutagenesis of basidiospores of Hypsizygus marmoreus generated new mushroom strains. The basidospores were treated with methanesulfonate methylester, an alkylating agent, to yield 400 mutant monokaryotic mycelia. Twenty fast-growing mycelia were selected and mated each other by hyphal fusion. Fifty out of the 190 matings were successful (mating rate of 26.3%), judged by the formation of clamp connections. The mutant dikaryons were cultivated to investigate their morphological and cultivation characteristics. Mutant strains No. 3 and No. 5 showed 10% and 6% increase in fruiting body production, respectively. Eight mutant strains showed delayed and reduced primordia formation, resulting in the reduced production yield with prolonged cultivation period. The number of the fruiting bodies of mutant No. 31, which displayed reduced primordial formation, was only 15, compared to the parental number of 65. Another interesting phenotype was a fruiting body with a flattened stipe and pileus. Dikaryons generated by mating with the mutant spore No. 14 produced flat fruiting bodies. Further molecular biological studies will provide details of the mechanism. This work shows that the chemical mutagenesis approach is highly utilizable in the development of mushroom strains as well as in the generation of resources for molecular genetic studies.

• 약학회지
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• 제42권5호
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• pp.507-512
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• 1998

In the course of developing novel antitumor intercalating agents. We synthesized 4-carbamoyloxymethyl-l-azaanthraquinones 7-12, incorporating the latent alkylating functi onality. These compounds were designed to explore the effect of substituent on the nitrogen of carbamate. The target compounds were prepared by hetero Diels-Alder reaction as a key step followed by functionalization of benzylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354; liver and MCF7; breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The compounds were less potent than doxorubicin against sensitive cell lines. However, the most active compound 12 was not cross-resistant with doxorubicin against KB-V-1.

• 약학회지
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• 제39권1호
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• pp.94-101
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• 1995

In order to evaluate the suppressive effects of galangin on the DNA damage induced by N-methyl-N-nitrosourea(MNU), in vitro sister chromatid exchange(SCE) test using Chinese Hamster ovary(CHO) cells was performed. Also the determinations of [$^{3}$H] MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action by galangin. MNU-induced SCEs were significantly decreased by simultaneous and pretreatment of galangin when S-9 mix was added only. In post-treatment, however, the MNU-induced SCEs were not decreased when S-9 mix was added or not. [$^{3}$H] MNU-induced total DNA binding was significantly inhibited by the treatment of galangin in calf thymus DNA and CHO cells. HPLC analysis of DNA hydrolysates shows that galangin caused a dose-dependant decrease in calf thymus DNA, but not significant decrease in CHO cells. These results suggest that the inhibition of galangin on the MNU-induced SCEs is due to the decrease of DNA binding and methylation with MNU. Therefore, galangin may be useful as a chemopreventive agent of alkylating agents.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.535-542
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• 1996

Seven isoazamitosene derivatives, mitomycin analogues, were synthesized and tested for cytotoxicities against leukemia and gastric cancer cell lines. Preparation of a pyrrolo[1, 2-a]benzimidazole (3) (azamitosene ring system) was completed by utilizing the Lewis acid-catalized cyclization, with .omicron.-chloronitrotoluene as the starting material. Nitration of 3 produced a mixtue of two isomers (5-nitro isomer (4) and 7-nitro isomer (5)) in product ratio of 36 : 52. 4 was directly converted into quinone (7) by reduction and Fremy oxidaton. Finally, quinone derivatives (8, 9, 10, and 11) were synthesized by 1, 4-addition of 7 with cyclic secondary amines. From above-mentioned 5, 8-nitro compound (15) was prepared in 4 steps. At pH 3, Fremy oxidation of 15 produced quinone (16), whereas iminoquinone derivatives (17a and 17b) at pH 7. Isoazamitosene derivatives (8, 9, 10, and 11), containing cyclic amino groups at the 7-position, showed potent cytotoxicity on P388, SNU-1, and KHH tumor cell lines. Among them, 8 had stronger cytotoxicity against SNU-1 cell line than mitomycin and adriamycin. Considering these results, isoazamitosene derivatives may had unique cytotoxicity profiles. However, isoiminoazamitosene derivatives (17a and 17b) revealed very weak cytotoxicity.

• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1457-1464
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• 2012

An ecofriendly catalytic route for selective synthesis of $N$-substituted azacyclopentanes, nitrogen-containing heterocyclic intermediates for many bioactive compounds, was established by carrying out $N$-heterocyclization (di $N$-alkylation) of primary amines with 1,4-dichloro butane (as dialkylating agent) using catalytic amount of hydrotalcite as solid base catalyst. The hydrotalcite was found to be efficient solid base catalyst for di $N$-alkylation of different primary amines (aniline, benzyl amine, cyclohexyl amine and n-butyl amine) giving 82 to 96% conversion (at optimized reaction condition) of 1,4-dichloro butane and > 99% selectivity of respective $N$-substituted azacyclopentanes within 30 min. under solvent free condition. The reaction parameters significantly influence the conversion of 1,4-dichloro butane to $N$-substituted azacyclopentanes. The nature of substituent present on amino group affects the reactivity of amine substrates for di $N$-alkylation reaction with 1,4-dichloro butane. The 1,4-dichloro butane was found to be highly reactive alkylating agent for di $N$-alkylation of amines as compared to 1,4-dihydroxy butane. The reusability of the catalyst and its chemical stability in the reaction was demonstrated.