protective effects of demethoxyviridine and 1-alpha-hydroxy-demethoxyviridine in the livers of male rats treated with diethylnitrosamine and 2-acetylaminflourene

To determine the protective effects of a fungal metabolite of demethoxyviridine [DMV] and its derivative, 1-alpha-hydroxy-DMV in the livers of 2-month-old male Spraque-Dawley rats treated with diethylnitrosamine [DEN] and 2-acetylaminflourene [2-AAF]. This study was performed in the Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey from May 2006. Animals were divided into 10 groups. Those were the control, olive oil, dimethyl sulfoxide [DMSO], DMV, 1-alpha-hydroxy-DMV, DEN, 2-AAF, DEN+2-AAF, DEN+2-AAF+DMV, and DEN+2-AAF+1-alpha-hydroxy-DMV-treated animal groups. The liver microsomes were prepared from rats and the levels of expression of cytochrome P450 1A2 [CYP1A2] enzymes were determined with western blot technique. The liver tissue slides were evaluated histopathologically with hematoxylin and eosin staining and immunohistochemically for Harvey-retrovirus associated DNA sequences [Ha-Ras], glutathione S- transferase [GST-p], and connexion-32 [Cx32] proteins. Notably, there were no appreciable differences in CYP1A2 level among control, olive oil, and DMSO-treated animals. The CYP1A2 level was significantly decreased in 2-AAF, DEN+2-AAF, DEN, DEN+2-AAF+DMV, DEN+2-AAF+1-alpha-hydroxy-DMV, 1-alpha-hydroxy-DMV, and DMV-treated animals as compared to the control. Most prenoplastic focus was found in DEN+2-AAF treated group. Demethoxyviridine and 1-alpha-hidroksi-DMV had protective effect in the livers of DEN, 2-AAF and DEN+2-AAF induced rats

Anticarcinogenic Effect of Red Ginseng on the Development of Liver Cancer Induced by Diethylnitrosamine in Rats

Anticarcinogenic effect of red ginseng (Panax ginseng C.A. Meyer cultivated in JiLin, China) on the development of liver cancer induced by diethylnitrosamine (DEN) in rats was studied, especially in preventive and curative groups. In the preventive group, the rats were given with DEN concomitantly with red ginseng fluid, and in the curative group, the rats were administered with red ginseng fluid after they developed liver cancer nodules induced by DEN. The result of the preventive group revealed that the developmental rate of liver cancer in the experimental group was 14.3%, while 100% in the control group, with the difference being statistically significant. DNA, RNA, glycogen, gamma-GT, SDH, and 5'-NT were maintained at relatively normal level in experimental group, and decreased or increased in the control group. The result of curative group showed that hepatoma nodules of the DEN-red ginseng group I were smaller than those of control group I, the structure of hepatic tissue was well preserved, the area with gamma-GT positive was smaller, and the ultrastructure of hepatocytes was normal. The average life span the DEN-red ginseng group II and the DEN control group II were 72.8 and 42.3 days, respectively. To sum up, all findings on preventive and curative groups had clearly proved that the red ginseng had the anticarcinogenic effect on the development of liver cancer induced by DEN in rats.

Avaliação do efeito da cafeína na carcinogênese esofágica induzida pela Dietilnitrosamina: estudo experimental em camundongos / Effect of caffeine on diethylnitrosamine-induced esophageal carcinogenesis in mice

Não existe consenso quanto à relação da cafeína com as neoplasias. O carcinoma epidermóide do esôfago é neoplasia de elevada incidência em nosso meio. Entre os fatores de risco conhecidos estão o tabagismo, o alcoolismo e bebidas ingeridas em temperaturas elevadas: chá, chimarrão, entre outras. Na literatura, não encontramos estudos sobre a cafeína e o câncer de esôfago. Objetivos: Avaliar o efeito da cafeína no CEE, utilizando modelo experimental de carcinogênese esofágica induzido pela DEN em camundongos e também o efeito da cafeína ingerida isoladamente sobre a mucosa do esôfago...

Carcinoma epidermóide de esôfago induzido pela dietilnitrosamina (DEN) / The epidermoid carcinoma of the esophagus induced by diethylnitrosamine

O objetivo desta pesquisa foi verificar a ocorrência de carcinoma epidermóide de esôfago induzido pela DEN, em ratos WISTAR. A DEN foi administrada a dois grupos de 20 animais (peso 250-300 grs.), na água de beber (10 mg/Kg/pêso) durante 72 hs/semana, respectivamente por 120 dias e 200 dias (T120 e T200). Outros 10 animais ingerindo apenas água serviram de controles. Os 50 animais foram sacrificados e seus esôfagos estudados macro e microscopicamente. No grupo controle nao ocorreram carcinomas, nem lesoes pré-neoplásicas. Nos grupos T120 e T200 ocorreram, respectivamente, 47 e 58 carcinomas, "in situ"; 1 e 20 carcinomas submucosos (p<0,05); 4 e 17 carcinomas micro-invasivos (p<0,05); 4 e 11 carcinomas avançados (p<0,05); 1 e 1 hiperplasias benignas. Além disso, foram encontrados carcinomas pulmonares e hepáticos. A maioria das lesoes macroscópicas avançadas no grupo T200 foram polipóides, exofiticas e nao invasivas à microscopia. Este estudo permite concluir que a DEN é efetiva na carcinogênese do esôfago do rato WISTAR e que as lesoes sao dose dependentes.

Surgimento de tumores hepáticos e lesöes pré-neoplásicas em fígado de rato com uso de dietilnitrosamina nas fases de síntese e G1 do ciclo celular / Appearance of liver tumors and pre-neoplastic lesions in the liver of rats with the use of diethylnitrosamine in the G1-phase of the cell cycle

A proliferaçäo celular é um fator importante para a maior suscetibilidade a transformaçäo maligna da célula. Altas taxas de proliferaçäo de hapatócitos podem ser obtidas através de hepatectomia parcial. Com o uso de hidroxiuréia, uma populaçäo celular em proliferaçäo pode ser bloqueada na transiçäo da fase G1 para a fase de síntese. Este artifício permite obter altas taxas de sincronizaçäo celular em fígado de rato após hepatectomia e possibilita experiências com cancerígenos em fases específicas do ciclo celular. Com a finalidade de verificar o surgimento de tumores e de lesöes pré-neoplásicas no fígado de ratos submetidos a exposiçäo repetida de cancerígeno em uma mesma fase do ciclo celular, ratos Wistar foram submetidos a hepatectomia parcial e sincronizaçäo celular com hidroxiuréia. Dietilnitrosamina foi injetada por via intraperitonial na fase G1, quatro horas após a hepatectomia, e uma hora após a perfusäo continuada de dez horas com hidroxiuréia, na fase de síntese de DNA. Houve predomínio significante do surgimento de lesöes pré-neoplásicas e de tumores nos animais injetados com o cancerígeno na fase de síntese.

Development of altered hepatocyte foci by separate and combined treatments with radiation and diethylnitrosamine in neonatal rats

To establish an in vivo radiation carcinogenesis model using glutathione S-transferase placental form positive (GST-P+) hepatic foci, newborn rats were irradiated once by 0.5 Gy and 2 Gy of gamma ray or 0.15 Gy and 0.6 Gy of neutron with or without 0.05% phenobarbital (PB). When the rats were sacrificed at the 12th or 21st week, the incidence of GST-P+ foci induction by radiation alone was very low. The neutron was more sensitive than the gamma ray at week 12 and the reverse phenomenon was observed in the groups at week 21. PB combination showed an increased incidence of GST-P+ foci in gamma ray irradiated groups. The neutron irradiation combined with PB did not show any significant difference compared with the corresponding PB untreated groups. We also investigated the combined effect of diethylnitrosamine (DEN) and 0.75 Gy of gamma ray irradiation. Intraperitoneal injection of 0.15 mumol/g body weight of DEN at 1 hour after gamma ray irradiation showed significantly increased the number and area of GST-P+ foci compared with those of DEN alone or DEN at 1 hour before gamma radiation (P < 0.001). From these data, after more defined experiments, an in vivo radiation carcinogenesis model will be established by radiation alone or a combination of radiation and carcinogens.