mitomycin C

丝裂霉素 C
  • 文章类型: Journal Article
    目的:比较结膜下注射丝裂霉素C(MMC)与常规海绵应用MMC在小梁切除术中的长期安全性和有效性。
    方法:回顾性分析90例接受丝裂霉素C小梁切除术的98只眼,分为两组,1-海绵组(n=52)和2-注射组(n=46)。在第一天收集了后续数据,15天,一个月,三个月,六个月,一年,两年三年.对基线和随访数据进行分析和比较,以研究眼内压(IOP)的显着差异,抗青光眼药物(AGM)和最佳矫正视力(BCVA)的数量。P值<0.05被认为具有统计学意义。
    结果:第一组术前平均IOP为34.61±13.3mmHg,第二组为33.07±9.6mmHg,3年时下降至11.43±3.2和11.59±3.2mmHg(两组p<0.001),组间无显著差异。第一组和第二组的术前平均AGM数分别为2.28±0.8和2.42±0.7,三年时分别降至1.19±1.1(p=0.405)和0.88±0.9(p=0.001)。三年时,第一组的完全和总体成功率(完全合格)分别为59.3%和78.9%,第二组为60.9%和80.4%。并发症发生率无统计学差异,术后干预,以及两组的最终视觉结果。
    结论:结膜下注射MMC是一种安全有效的替代海绵应用,具有相当的长期手术效果。
    OBJECTIVE: To compare the long-term safety and efficacy of subconjunctival injection mitomycin C(MMC) with conventional sponge applied MMC during trabeculectomy.
    METHODS: Retrospective analysis of 98 eyes of 90 patients who underwent trabeculectomy with Mitomycin C were divided into two groups, group 1- sponge (n = 52) and group 2- Injection(n = 46). Follow-up data were collected on day one, day 15, one month, three months, six months, one year, two years and three years. Data from baseline and follow-up visits were analyzed and compared to study the significant difference in intraocular pressure (IOP), number of antiglaucoma medications (AGM) and best corrected visual acuity (BCVA) . P-value of <0.05 was considered statistically significant.
    RESULTS: Mean preop IOP was 34.61 ± 13.3 mmHg in group one and 33.07 ± 9.6 mmHg in group two, which reduced to 11.43 ± 3.2 and 11.59 ± 3.2 mmHg at three years (p < 0.001 in both groups) with no significant difference between the groups. Mean number of preoperative AGM was 2.28 ± 0.8 and 2.42 ± 0.7 in group one and two respectively which reduced to 1.19 ± 1.1(p = 0.405) and 0.88 ± 0.9(p = 0.001) at three years. Complete and overall success rates (complete + qualified) were 59.3% and 78.9% in group one and 60.9% and 80.4% in group two at three years. No statistically significant difference was found in complication rates, post-operative interventions, and final visual outcome in both groups.
    CONCLUSIONS: Subconjunctival Injection MMC was a safe and effective alternative to sponge application with comparable long term surgical outcomes.
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  • 文章类型: Journal Article
    目的:许多接受膀胱内BCG治疗的非肌层浸润性膀胱癌患者尽管最初有足够的反应,但复发率高。在这项研究中,对膀胱内化疗(CHT)联合丝裂霉素C(MMC)治疗后复发或不能耐受治疗且因任何原因不能接受根治性膀胱切除术的患者进行了评价.
    方法:59例接受完全膀胱肿瘤切除术的患者,谁有T1高级别肿瘤,在病理学中没有观察到变异的组织学,和以前接受过膀胱内BCG治疗的患者被纳入研究.应用膀胱内CHT-MMC辅助治疗。作为一种治疗方案,诱导每周一次,持续6周,随后以4周的间隔进行6次维持治疗。每次治疗,它涉及温度高达42℃±2的膀胱壁热疗,并以30分钟的间隔两次膀胱内给药20mg/50mlMMC溶液。
    结果:热丝裂霉素后的无复发生存率分别为58.7%和48%,分别,在24个月和44个月,无进展生存率为72.6%和66.2%,分别。在根据诊断时肿瘤数量进行的亚组分析中(单个,2-5,超过5),无复发生存率为81.8%,48.2%和11%,分别,中位随访期44个月.
    结论:膀胱内CHT-MMC可被视为对BCG无反应或对BCG不耐受的非肌肉浸润性乳头状尿路上皮癌患者的替代治疗。需要对更多患者进行前瞻性设计的研究。
    OBJECTIVE: Many patients receiving intravesical BCG treatment for non-muscle-invasive bladder cancer experience high recurrence rates despite initial adequate response. In this study, the effectiveness of intravesical chemohyperthermia (CHT) with mitomycin C (MMC) was evaluated in patients who developed relapse after intravesical BCG treatment or could not tolerate the treatment and could not undergo radical cystectomy for any reason.
    METHODS: 59 patients who underwent complete bladder tumour resection, who had a T1 high-grade tumour and no variant histology was observed in the pathology, and who had previously received intravesical BCG treatment were included in the study. Adjuvant treatment with intravesical CHT-MMC was applied. As a treatment protocol, induction was applied once a week for 6 weeks, followed by maintenance treatment 6 times at 4-week intervals. Each treatment session, it involved bladder wall hyperthermia with a temperature of up to 42 ℃ ± 2 and intravesical administration of 20 mg/50 ml MMC solution twice at 30-min intervals.
    RESULTS: Recurrence-free survival after warm mitomycin was 58.7 and 48%, respectively, at 24 months and 44 months, and progression-free survival was 72.6 and 66.2%, respectively. In the subgroup analysis performed according to the number of tumours at diagnosis (single, 2-5, more than 5), recurrence-free survival rates were 81.8%, 48.2% and 11%, respectively, during the median follow-up period of 44 months.
    CONCLUSIONS: Intravesical CHT-MMC can be considered as an alternative treatment in selected well-informed patients with non-muscle-invasive papillary urothelial carcinoma who are unresponsive to BCG or intolerant to BCG. Prospectively designed studies with larger number of patients are needed.
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  • 文章类型: Case Reports
    范可尼贫血是一种罕见但最普遍的遗传性再生障碍性贫血,主要以常染色体隐性方式传播,除了一个X连接的变体。它来自16个不同互补组的基因突变,这对DNA稳定性至关重要。它的特点是广泛的先天性畸形,进行性全血细胞减少症,血液系统恶性肿瘤和实体瘤的风险增加。与之相关的先天性异常可以影响各种器官系统,包括骨骼系统,患者之间有显著的变异性。这里报道了一个类似的病例,具有典型的FA临床特征。由于不同的表型表现,诊断FA可能具有挑战性。使用丝裂霉素C(MMC)或二环氧丁烷(DEB)的染色体破坏研究是一种独特的细胞标记,有助于诊断。
    Fanconi anemia is a rare but most prevalent form of inherited aplastic anemia, predominantly transmitted in an autosomal recessive manner, except for one X-linked variant. It arises from mutations in the genes across 16 different complementation groups that are crucial for DNA stability. It is marked by a wide range of congenital malformations, progressive pancytopenia, and an increased risk of both hematological malignancies and solid tumors. The congenital abnormalities associated with it can affect various organ systems, including the skeletal system, with significant variability among patients. One similar case has been reported here, which had the typical clinical features of FA. Due to varied phenotypic presentation, diagnosing FA can be challenging. A Chromosomal Breakage Study using mitomycin C (MMC) or diepoxybutane (DEB) is a distinctive cellular marker that aids in the diagnosis.
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  • 文章类型: Journal Article
    背景:增加膀胱内化疗剂渗透度的装置正在成为经典卡介苗(BCG)治疗的替代品。
    目的:比较丝裂霉素C与电动给药装置(MMC-EMDA)和卡介苗在无原位癌(CIS)的中高危非肌层浸润性膀胱癌(NMIBC)患者中的疗效。
    方法:前瞻性非随机研究,其中47例患者接受MMC-EMDA(40mgMMC在50mg蒸馏水中稀释,20mA,30分钟。每周6次,然后每月6次滴注),48例患者接受BCG(50mgOncoCITE®在50ml生理盐水中稀释60分钟。每周滴注6次,然后在第3、6和12个月滴注3次)。主要终点是24个月时的无复发率(RFR)。次要终点是24个月随访时的复发时间和无进展率(PFR)。
    结果:两组患者的基线评估和平均随访时间相似(MMC-EMDA组:26.4个月;BCG组:28.4个月(p=0.44))。24个月时,MMC-EMDA组的RFR为80.9%,BCG组为77.1%(p=0.969)。MMC-EMDA组的平均复发时间为12.5个月,BCG组为14个月(p=0.681)。24个月时,MMC-EMDA组的PFR为97.9%,卡介苗组为93.8%(p=0.419)。
    结论:在没有CIS的高危和中危NMIBC患者中,MMC-EMDA和BCG治疗没有差异。
    BACKGROUND: Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment.
    OBJECTIVE: To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS).
    METHODS: Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up.
    RESULTS: Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419).
    CONCLUSIONS: No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.
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  • 文章类型: Journal Article
    建立大鼠血浆中丝裂霉素C的液相色谱-串联质谱(LC-MS/MS)测定方法,样品使用固相萃取处理,内标是卡马西平.反相C18柱用于LC-MS/MS研究,并且以0.3mL/min的速率将由在乙腈中的0.1%甲酸和水组成的流动相注入其中。使用前体产物离子对335.3→242.3(丝裂霉素C)和237.1→194.1(卡马西平)的正离子模式进行多反应监测,以定量化合物。血浆中的线性范围为10-4000ng/mL(r2=0.992)。批间和批内精密度分别为<14.3%(LLOQ:14.7%)和13.4%(LLOQ:16.1%),分别。血浆中丝裂霉素C的回收率和基质效应分别为113%和111%,分别。丝裂霉素C在该测定方法的条件下是稳定的。最后,这种方法在对大鼠静脉和口服丝裂霉素C的药代动力学研究中被证明是有效的。
    To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1 % formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 → 242.3 (mitomycin C) and 237.1 → 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10-4000 ng/mL (r2 = 0.992). The inter-batch and intra-batch precision were <14.3 % (LLOQ: 14.7 %) and 13.4 % (LLOQ: 16.1 %), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113 % and 111 %, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.
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  • 文章类型: Case Reports
    报告3例孤立性角膜上皮内瘤变(CIN)的临床特征和治疗结果。
    本病例系列介绍了3例孤立的CIN。收集的数据包括,表现出包括视力在内的体征和症状,眼前段检查,治疗后就诊失败时的内科和外科结果以及体征和症状。
    病例1是一名45岁的男性,患有孤立的灰色变形虫角膜病变,该病变通过酒精辅助上皮切除术切除,他还接受了6个周期的局部用丝裂霉素C(MMC)0.02%和1次注射干扰素α-2b,在10年随访期间没有复发.病例2为78岁男性,因可疑白色角膜病变被完全切除,患者还接受了6次结膜下注射干扰素α-2b.然而,病变在治疗后2.5年复发。病例3是一名63岁的男性患者,其表现为使用酒精辅助上皮切除术切除的孤立性角膜病变。在6个月的最后一次随访时,患者接受了4个周期的局部用5-氟尿嘧啶治疗,没有复发.
    孤立的角膜上皮内瘤变(CIN)是一种罕见的实体,在文献中报道的病例很少。在这个系列中,我们报告了孤立性CI的联合手术和药物治疗的长期和短期管理结果。
    UNASSIGNED: To report clinical features and treatment outcome of three cases with isolated corneal intraepithelial neoplasia (CIN).
    UNASSIGNED: This case series presents 3 patients with isolated CIN. Data collected included, presenting signs and symptoms including vision, anterior segment examination, medical and surgical outcomes and signs and symptoms at lost post-treatment visit.
    UNASSIGNED: Case 1 was a 45-year-old male who presented with an isolated grayish amoeboid corneal lesion which was excised with alcohol assisted epitheliectomy, he also received 6 cycles of topical mitomycin C (MMC) 0.02% and one injection of interferon alfa-2b with no recurrence during the 10-year follow-up period. Case 2 was 78-year-old male referred for a suspicious white corneal lesion which was completely excised, the patient also received 6 subconjunctival injections of interferon alpha-2b. However, the lesion recurred at 2.5-years post-treatment. Case 3 was a 63-year-old male patient who presented with an isolated corneal lesion that was excised using alcohol-assisted epitheliectomy, patient received four cycles of topical 5-fluorouracil with no recurrence at last follow-up visit at 6 months.
    UNASSIGNED: Isolated corneal intraepithelial neoplasia (CIN) is a rare entity with few reported cases in the literature. In this case series, we report long and short-term management outcomes of combined surgical and medical therapy for isolated CIN.
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  • 文章类型: Journal Article
    背景:对腹膜假性黏液瘤的细胞减灭术的长期有利结果的绝对要求是完全切除所有可见的疾病。要做到这一点,需要结合顶叶周围切除术和内脏切除术。细胞减灭术辅以腹腔热化疗。
    方法:我们搜索了我们的数据库并确保了需要进行全胃切除术和全结肠切除术以实现完整的细胞减灭术的患者的文件。确定了低度粘液性肿瘤(LAMN)和粘液性阑尾腺癌(MACA)组织学的存活率。评估临床和组织学变量对生存率的影响。
    结果:450例LAMN组织学患者中有13例(2.9%),186例MACA组织学患者中有14例(7.5%)进行了内脏切除。这27例患者的中位生存期为10年。LAMN和MACA患者的生存率相同。对于LAMN组织学,这种广泛内脏切除的要求显著降低了生存率(p<0.0001).对于MACA,对生存率无不良影响(p=0.4359).4类不良事件导致生存率降低(p=0.0014)。
    结论:晚期腹膜假性黏液瘤的10年中位生存期伴随全胃切除术加结肠切除术。全身化疗和4类不良事件降低了生存率。
    BACKGROUND: The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy.
    METHODS: We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival.
    RESULTS: Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014).
    CONCLUSIONS: A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.
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  • 文章类型: Journal Article
    丝裂霉素C(MMC)具有抗肿瘤作用,被认为是一种广谱抗生素。四君子汤(SJZD),一个著名的中国古代处方,与化疗药物联合治疗癌症时被广泛使用。研究表明,SJZD可以与其他药物联合使用,增强对癌症的治疗效果,抑制化疗药物的毒性,但具体机制尚不清楚。因此,我们希望进一步探讨SJZD和MMC联合的抗肿瘤机制。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴化物测定,流式细胞术,westernblot,使用1HNMR和HPLC-MS在细胞水平上研究机制。结果表明,联合给药对抑制癌细胞增殖有更显著的效果,促进它们的凋亡。基于代谢组学,在MMC组中发现38种生物标志物,在联合给药组中发现43种生物标志物。其中,在联合给药组中发现了18种独特的生物标志物。研究表明,联合给药的抗肿瘤机制与氨基酸代谢有关,能量代谢,脂质代谢和核苷酸代谢,其中氨基酸代谢是最重要的。此外,SJZD通过提高机体免疫力和改善氧化应激环境达到减毒增效的效果。
    Mitomycin C (MMC) has an antitumor effect and is considered as a broad-spectrum antibiotic. Sijunzi Decoction (SJZD), a well-known ancient Chinese prescription, is widely used in the treatment of cancer when combined with chemotherapy drugs. Studies have shown that SJZD can be combined with other drugs to enhance the therapeutic effect against cancer and inhibit the toxicity of chemotherapy drugs, but the specific mechanism is not clear. Thus, we hope to further explore the antitumor mechanism of combined SJZD and MMC. 3-(4,5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, western blot, 1H NMR and HPLC-MS were used to study the mechanism at the cellular level. The results show that the combined administration can have a more significant effect on inhibiting the proliferation of cancer cells, promoting their apoptosis. Based on metabolomics, 38 biomarkers were found in the MMC group and 43 biomarkers were found in the combined administration group. Among them, 18 unique biomarkers were discovered in the combined administration group. Studies have shown that the antitumor mechanism of combined administration is related to amino acid metabolism, energy metabolism, lipid metabolism and nucleotide metabolism, among which amino acid metabolism is the most important. In addition, SJZD achieves the effect of toxin reduction and efficiency enhancement by improving the body\'s immunity and improving the oxidative stress environment.
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  • 文章类型: Journal Article
    目的:建议膀胱内灌注丝裂霉素C(MMC)以预防中危非肌层浸润性膀胱癌(IR-NMIBC)的复发;然而,最佳治疗方案和剂量尚不确定.我们的目的是评估辅助MMC的有效性,并比较不同的MMC方案预防复发。
    方法:我们在PubMed中进行了全面的搜索,Scopus,和WebofScience于2023年11月进行的研究,调查接受辅助MMC的IR-NMIBC患者的无复发生存率(RFS)。使用不同MMC方案或其他膀胱内药物作为对照的前瞻性试验被认为是合格的。
    总的来说,14项研究有资格进行系统评价,11项研究有资格进行RFS的荟萃分析。估计一年,2年,5年RFS率为84%(95%置信区间[CI]79-89%),75%(95%CI68-82%),接受MMC诱导加维持治疗的患者为51%(95%CI40-63%),和88%(95%CI83-94%),78%(95%CI67-89%),接受卡介苗(BCG)维持治疗的患者占66%(95%CI57-75%),分别。对于40mgMMC(2项研究),MMC维持方案的2年RFS率估计为76%(95%CI69-84%),对于30mgMMC(4项研究)为66%(95%CI60-72%)。在包括的研究中,卡介苗维持提供了与维持40mgMMC相当的2年RFS(78%对76%)。RFS在MMC维持时间上没有差异(>1年vs1年vs<1年)。
    结论:MMC诱导和维持方案提供的短期RFS率与IR-NMIBC中BCG维持的RFS率相当。对于佐剂诱导和维持,40毫克的MMC似乎比30毫克更有效地预防复发。我们没有观察到长期维持方案的RFS益处。
    结果:对于中危非肌层浸润性膀胱癌患者,用称为丝裂霉素C(MMC)的药物进行膀胱治疗似乎与卡介苗(卡介苗)一样有效,可以预防肿瘤切除后的复发。需要进一步的试验以获得关于最佳MMC剂量和治疗时间的更强有力的证据。
    OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence.
    METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible.
    UNASSIGNED: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr).
    CONCLUSIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens.
    RESULTS: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.
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  • 文章类型: Journal Article
    细胞遗传学研究表明,人类染色体1,9和16,具有高度甲基化的经典卫星DNA的大异色区域,丝裂霉素C(MMC)容易诱导染色单体断裂和互换。几项研究表明,来自9号染色体以及可能来自1号和16号染色体的物质优先被MMC微核化。这里,我们进一步检查了MMC对微核(MN;有或没有细胞松弛素B)和染色体畸变(CA)的染色体特异性诱导。处理来自两名男性供体的分离的人淋巴细胞的培养物(在培养48小时时,24小时)与MMC(500ng/ml),并通过9号染色体的pancentromericDNA探针和油漆探针以及1号和16号染色体的油漆探针检查诱导的MN。MMC使MN的总频率增加了6-8倍,但9号染色体阳性(9)MN的频率增加了29-30倍,1号染色体阳性(1)MN和16号染色体阳性(16)MN的频率增加了12-16倍和10-17倍,分别。用MMC治疗后,所有MN的34-47%为9+,17-20%1+,和3-4%16+。9MN中的大多数(94-96%)不含着丝粒,因此带有无心片段。当MMC诱导的CAs畸变通过使用9号染色体的经典卫星区域和长臂和短臂端粒的探针和探针来表征时,染色体断裂的比例很高(31%)和互换(41%)涉及9号染色体。在83%的案例中,9号染色体上的断点正好在经典卫星探针标记的区域(9cen-q12)下方。我们的结果表明,MMC特异性诱导携带9号、1号和16号染色体片段的MN。9号染色体的CA在MMC处理的淋巴细胞的中期中高度过量。优先断点低于9q12区域。
    Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6-8-fold but the frequency of chromosome 9 -positive (9+) MN by 29-30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12-16-fold and 10-17-fold, respectively. After treatment with MMC, 34-47 % of all MN were 9+, 17-20 % 1+, and 3-4 % 16+. The majority (94-96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12.
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