Aspirin intake suppresses MMC-induced genotoxicity in mice.

The genotoxicity induced by mitomycin C (MMC) was found to be decreased by aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were administered and then liver, lung, kidney, spleen, colon and bone marrow were sampled after 3 h. Significant protective effects of aspirin against MMC-induced genotoxicity was observed in all but the bone marrow, where no change was evident. The results suggest that the radical scavenging ability of aspirin prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.

Absence of antimutagenicity of Cochlospermum regium (Mart. and Schr.) Pilger 1924 by micronucleus test in mice

Cochlospermum regium (Mart. and Schr.) Pilger, popularly known as "algodãozinho do campo", is a medicinal plant that grows in the Cerrado of Brazil. This plant has been used in traditional medicine against various diseases such as leucorrhoea, gastritis and ulcers. It has also been effective in treating skin problems like pimples, boils and blotches. In the present study, the in vivo antimutagenicity of aqueous extract of C. regium was evaluated. The Micronucleus Test was performed in polychromatic erythrocytes from Swiss male mice treated with one of the four doses of extract of the plant (19, 38, 76 and 114 mg.kg-1 body weight), administered by intraperitonial injection (i.p.) simultaneously with cyclophosphamide (24 mg.kg-1 b.w.) or mitomycin C (4 mg.kg-1 b.w.). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed no significant reduction of the micronucleated polychromatic erythrocytes frequency (P > 0.05). In conclusion, the data indicate that C. regium roots aqueous extract, for the conditions used, did not exhibit the antimutagenic effect.

Cochlospermum regium (Mart. & Schr.) Pilger, conhecido popularmente como "algodãozinho-do-campo", é uma planta medicinal que cresce no Cerrado brasileiro. Esta planta tem sido utilizada na medicina tradicional contra várias doenças como leucorréia, gastrites e úlceras. Esta também tem se mostrado efetiva no tratamento de doenças de pele como espinhas, furúnculos e manchas. No presente estudo, foi avaliada a antimutagenicidade do extrato aquoso de C. regium pelo Teste do Micronúcleo in vivo. Este ensaio foi realizado em eritrócitos policromáticos de camundongos machos Swiss tratados com quatro concentrações diferentes do extrato da planta (19, 38, 76 e 114 mg.kg-1 por peso corpóreo), administrado por injeção intraperitonial (i.p.) simultaneamente com ciclofosfamida (24 mg.kg-1 p.c.) ou mitomicina C (4 mg.kg-1 p.c.). A citotoxicidade foi avaliada pela razão eritrócitos policromáticos e normocromáticos (PCE/NCE). Os resultados obtidos não mostraram redução significativa da freqüência de eritrócitos policromáticos micronucleados (P > 0,05). Em conclusão, os resultados indicam que o extrato aquoso de raiz de C. regium, para as condições utilizadas, não exibiu efeito antimutagênico.

study comparing two different combination chemotherapy protocol in metastatic breast cancer patients previously treated with anthracycline chemotherapy regimen

Treatment for systemic disease is palliative in intent. Goals of treatment include improving quality of life and prolongation of life. Although median survival has been reported to be 18 to 24 months, some patients experience long-term survival. Several combination chemotherapy has been used with comparable results. Quality of life and cost of treatment are an important factor to determine the best combined chemotherapy. In this study. To compare a Taxane based regimen versus If osphamide fluorouracil and mitomycin combined regimen [FILM]. This study was designed to recruit a total of 52 patients with metastatic breast cancer who has received anthracycline chemotherapy in their initial treatment and were randomized between 4 cycles of FILM chemotherapy [Group A] or Taxane based chemotherapy [Group B] to be given every 3 weeks. Patients were assessed for response and toxicity, statistical analysis was used to estimate survival and disease control. Between January 2006 and January 2007, a 52 female patients with metastatic breast cancer have been randomized to either Taxane based or FILM [26 patients in each arm]. Patients were evenly distributed as regards age, staging at first diagnosis, chemotherapy that was previously used, hormonal receptors status and Her-2, and sites of metastases. All patients received the planned treatment. As regards response rate, overall response rate was 73% for group A and 92% for group B P= .047. Progression free survival was better in taxan based regimen 7.3 +/- 3.4 than FILM based 5.6 +/- 2.8 the difference was statistical significant with P= .02. On the other hand, cost of treatment was extremely higher for group B than group A. The cost of treatment was significantly higher in taxan group than FILM P 0.00002. There was no significant difference in quality of life in both groups. Taxan based chemotherapy is significantly better than FILM in terms of PFS. However, there was no significant difference as regards quality of life or overall survival. On the other hand, cost of treatment is significantly higher in Taxane based chemotherapy

Avaliação ultra-estrutural dos efeitos tóxicos da mitomicina C no epitélio ciliar de olhos de coelhos normais com e sem tratamento hipotensor ocular prévio / Ultrastructural evaluation of mitomycin C toxic effects on the ciliary epithelium of normal rabbits eyes with and without aqueous humor suppressant treatment

OBJETIVO: Avaliar o epitélio ciliar interno (ECI) do corpo ciliar após aplicação de mitomicina C (MMC) sob retalho escleral, em animais tratados com dois tipos de inibidores da produção do humor aquoso. MÉTODOS: Foram estudados ambos os olhos de 16 coelhos divididos em 4 grupos experimentais. Foi realizado retalho escleral em todos os olhos dos animais, mas apenas os olhos direitos (OD) receberam MMC. No grupo 1 (G1) não houve tratamento prévio. Nos grupos G2 e G4 foi administrada acetazolamida e nos grupos G3 e G4 maleato de timolol. O ECI foi examinado à microscopia eletrônica de transmissão (MET). Os olhos esquerdos formaram os grupos controle. RESULTADOS: Em todos os grupos exceto no G1 OE, foram observadas: retração das células e/ou alargamento entre invaginações, mitocôndrias com rarefação, vesículas claras e corpos densos. A membrana limitante interna estava espessada, descontínua ou descolada em todos grupos exceto G1 OE e G2 OE. Foi observada liberação de material citoplasmático apenas nos grupos tratados com inibidores da produção de humor aquoso. CONCLUSÕES: 1- MMC, acetazolamida e maleato de timolol causaram alterações morfológicas no epitélio ciliar mesmo usados isoladamente. 2- A associação MMC e acetazolamida causou mais alterações do que a acetazolamida isoladamente, mas não mais do que a MMC isoladamente. 3- Nas demais associações as alterações foram semelhantes.

PURPOSE: To evaluate the effects of mitomycin C (MMC) on the internal ciliary epithelium (ICE) of the ciliary body of animals treated with two differents aqueous humor supressants. METHODS: The eyes of sixteen Norfolk albino rabbits divided into four experimental groups were studied. The right eyes (RE) of the four groups received 0.1 ml of MMC (0.5 mg/ml) under the scleral flap. The left eyes (LE) was the control group. Group 1 (G1) did not have any other treatment. To Group 2 (G2) and Group 4 (G4) acetazolamide was administered. To Group (G3) and Group 4 (G4) timolol maleate was administered. ICE was examined by transmission electron microscopy (TEM). RESULTS: The following aspects were observed in all groups, except in G1 LE: cell shrinkage and/or enlargement of intercellular spaces, rarefied mitochondria, clear vesicular structures and electron-dense bodies. The internal limitant membrane showed to be thickened, discontinued and separeted in all groups, except in G1 LE and G2 LE. Discharge of cytoplasmatic material was observed only in the groups treated with aqueous humor supressants. CONCLUSIONS: 1) MMC, acetazolamide and timolol maleate caused morphological alterations in the ciliary epithelium even when used alone. 2) The combination of MMC and acetazolamide caused more alterations than did isolated acetazolamide, but not more than MMC alone. 3) For the other combinations the alterations were similar.

Toxicidade da mitomicina C no epitélio corneano de coelhos / Mitomycin C toxicity in the corneal epithelium of rabbits

OBJETIVO: Avaliar os efeitos do uso tópico da mitomicina C a 0,02 por cento, no epitélio íntegro da córnea de coelhos, sob o ponto de vista histopatológico. MÉTODOS: A mitomicina C a 0,02 por cento (olhos esquerdo) e água destilada (olhos direito, controle) foram instiladas, 4 vezes ao dia, por 14 dias, nos olhos de 28 coelhos, na superfície ocular íntegra. Os animais foram sacrificados no 15º, 50º e 100º dia de experimento. O exame histopatológico do epitélio corneano foi complementado por análise morfométrica, que pelo método de contagens de pontos, estudou área do epitélio, número de núcleos, relação núcleo-citoplasma, área da célula epitelial, área do núcleo e área do citoplasma, na região do limbo e central da córnea. RESULTADO: O uso de mitomicina C não desencadeou alterações histopatológicas no epitélio corneano, observando-se a continuidade do epitélio, as células epiteliais se apresentaram dispostas de maneira ordenada, com número de camadas obedecendo a maturação normal e ausência de atipia celular. A análise morfométrica demonstrou alterações significativas nas diferentes estruturas do epitélio, na região do limbo e central da córnea, principalmente nas áreas estimadas do epitélio, do citoplasma e do número de núcleos, verificando-se hipertrofia da célula epitelial, redução da relação núcleo-citoplasma e diminuição do número de núcleos. Estes valores voltaram próximos ao nível controle no 100º dia de avaliação. CONCLUSAO: Os resultados desta investigação demonstraram baixo potencial tóxico do uso da mitomicina C na superfície ocular íntegra de coelhos, nessa dosagem e concentração.

Dark variants of luminous bacteria whole cell bioluminescent optical fiber sensor to genotoxicants / 华中科技大学学报（医学）（英德文版）

A stable dark variant separated from photobacterium phosphoreum (A2) was fixed in agar-gel membrane and immobilized onto an exposed end of a fiber-optic linked with bioluminometer. The variant could emit a luminescent signal in the presence of genotoxic agents, such as Mitomycin C (MC). The performance of this whole-cell optical fiber sensor system was examined as a function of several parameters, including gel probe thickness, bacterial cell density, and diameter of the fiber-optic core and working temperature. An optimal response to a model genotoxicant, Mitomycin C, was achieved with agar-bacterial gel membrane: the thickness of gel membrane was about 5 mm; the cell density of bacteria in gel membrane was about 2.0 x 10(7)/ml; the diameter of fiber-optic core was 5.0 mm; the working temperature was 25 degrees C. Under these optimized conditions, the response time was less than 10 h to Mitomycin C, with a lower detection threshold of 0.1 mg/L.

Efficiency of Coleus aromaticus extract in modifying cyclophosphamide and mitomycin-C induced clastogenicity in mouse bone marrow cells.

The anticlastogenic potency of the ethanolic extract of a medicinal plant, C. aromaticus was investigated by taking bone marrow chromosomal aberration assay and micronucleus (MN) test as the test parameters. Swiss albino mice were fed orally with different doses (10,15, 25, 50 and 100 mg/kg body weight) of ethanolic extract for 7 days and on the 7th day, two doses each of anticancer drugs cyclophosphamide (CP; 25 and 50 mg/kg body weight) and mitomycin-C (MMC; 4 and 8 mg/kg body weight) were injected, ip, to different groups of animals. Bone marrow MN preparations were made at 24 and 48 hr time intervals. Coleus extract reduced CP and MMC induced MN and lower doses of the extract were found to be more effective than higher doses. The effective doses of extract in MN test were selected to study the anticlastogenic effects against CP (25 and 50 mg/kg body weight) and MMC (2 and 4 mg/kg body weight) induced chromosomal aberrations. The results indicate the protective effect of C. aromaticus against CP and MMC induced cytogenetic damage.

Efeitos do uso do colirio de mitomicina C na superficie ocular de coelhos / Effects of use of mitomycin C on ocular surface in rabbits eyes

Proposito: Investigar os efeitos do uso topico de mitomicina C (MMC), na contagem de celulas caliciformes e no tipo de infiltrado celular inflamatorio, na conjuntiva ocular de coelhos. Metodos: coelhos de raca California receberam duas gotas de MMC (0,2mg/ml) quatro vezes por dia (n=15) ou agua destilada (n=5) por 14 dias. Exames biomicroscopicos foram realizados durante 25 dias. Especimens de conjuntiva para exame histopatologico foram obtidos apos a suspensao do uso de MMC nos dias 1 (n=5), 36 (n=5) e 86 (n=5) e foram processados para microscopia de luz corados com HE e PAS. A contagem de celulas caliciformes PAS-positiva foi realizada em campos de 400 aumentos em cada amostra. Resultados: Hiperemia conjuntival foi observada no quarto dia de instilacao de MMC e persistiu por 7 dias apos a suspensao da droga.

Evaluación in vitro de la viabilidad y proliferación de fibroblastos de la Cápsula de Tenon humana: expuestos a 5-fluorouracilo y mitomicina C / Evaluation in vitro of the viability and proliferation of fibroblasts of Human Tenon capsule: expose to 5-fluororacil and mitomicyn C

En este trabajo reportamos los resultados de un estudio prospectivo acerca del efecto del 5-Fluorouracilo (5-Fu) y la Mitomicina C (MMC) sobre los fibroblastos provenientes de la cápsula de Tenon humana. El estudio fue realizado en pacientes del Servicio de Oftalmología del Hospital "F.A. Rísquez", Caracas, Venezuela. Los fibroblastos cultivados y expuestos a 5-FU y MMC en diferentes concentraciones y con diferentes tiempos de exposición. La viabilidad celular fue evaluada por el método del MTT y la proliferación de fibroblastos fue estudiada por cintaje celular con la cámara de Newbauer. Encontramos que la toxicidad celular fue mayor con el uso de la MMC que con el 5-FU, pero nunca mayor del 30 por ciento. La citotoxicidad relacionada con la concentración del 5-FU fue 12,7 por ciento a 14,3 por ciento en comparación con una citotoxicidad de 8.8 a 20.5 por ciento de la MMC. La citotoxicidad del 5-FU y la MMC fue directamente proporcional al tiempo de exposición. La inhibición de la proliferación de fibroblastos de la Cápsula de Tenon Humana fue mayor con la MMC que con el 5-FU. La toxicidad celular puede ser modulada más por la concentración de la droga que por el tiempo de exposición

Efeitos do uso tópico da mitomicina C em olhos de ratas / Effects of the topical use of mitomycin C in rat eyes

Realizaram-se 2 experimentos, um de 16 (1) e outro de 44 dias (II) para avaliar alteraçöes a nível de córnea e cristalino, variaçäo de peso corpóreo e desenvolvimento ocular decorrentes do uso tópico da mitomicina C em olhos de 79 ratas Wistar em crescimento. Foram utilizadas concentraçöes de 0,02 por cento, 0,04 por cento, 0,08 por cento e 0,16 por cento, 4 vezes ao dia por 14 dias. Observaram-se reaçäo blefaroconjuntival moderada e ceratite punctiforme difusa leve nos olhos que utilizaram as concentraçöes de 0,08 e 0,16 por cento, que se desenvolveram ao longo da segunda semana de uso e regrediram 5 dias após sua suspensäo. Os grupos que utilizaram as concentraçöes de 0,02; 0,04 por cento e controles (cloreto de sódio a 0,9 por cento), näo apresentaram estas manifestaçöes. Näo foi verificada variaçäo do peso corpóreo e dos olhos dos animais no período abrangido pelos experimentos, näo tendo sido detectadas alteraçöes histopatológicas, atribuídas ao uso tópico da mitomicina C