Antiproliferative role of Indigofera aspalathoides on 20 methylcholanthrene induced fibrosarcoma in rats

<p><b>OBJECTIVE</b>To find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats.</p><p><b>METHODS</b>Fibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied.</p><p><b>RESULTS</b>Fibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment.</p><p><b>CONCLUSIONS</b>The treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.</p>

Differentiation of rat bone marrow mesenchymal stem cells into adipocytes and blockage of the differentiation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the pathogenesis of tumors by blocking the normal differentiation process of stem cells.</p><p><b>METHODS</b>Bone marrow mesenchymal stem cells (BMSCs) from rats were isolated, cultured and purified by whole bone marrow adherence method. The rat BMSCs were induced to differentiate into adipocytes with dexamethasone, insulin and indomethacin. Blockage of the differentiation process was induced by 3-methylcholanthrene (3-MC).</p><p><b>RESULTS</b>The differentiation experiment showed that at 30 days after the induction, oil red O staining-positive cells occurred with increased intracytolasmic lipid droplets, characteristic for adipocytes. The differentiation blockage experiment showed that at 30 days after induction, the deposits of oil red O staining-cytoplasmic lipid droplets was significantly reduced, indicating that the blocked cells were adipocytes, but not fully differentiated. Morphological identification showed that cell contact inhibition disappeared, abnormal cell nuclei, increased number of micronucleus aberration and karyotype abnormalities, indicating that malignant transformation of the stem cells occurred after the differentiation blockage.</p><p><b>CONCLUSIONS</b>The results of this study show a blockage of the differentiation of that stem cells at the intermediate phase, and a tendency of malignant transformation of the stem cells. The results of our study provide new evidence that cancer stem cells may be originated by suppression of stem cell differentiation.</p>

Reversión del eclipse inmunológico y vacunación terapéutica contra el cáncer en un modelo experimental / Reversion of the immunological eclipse and therapeutic vaccination against cancer in an experimental model

Aunque existen vacunas para prevenir la aparición de tumores en animales de experimentación, la mayoría de los intentos por aplicar aquellas vacunas con fines terapéuticos contra tumores establecidos no han sido exitosos. Para comprender la naturaleza de esta refractariedad, estudiamos un tumor de ratón fuertemente inmunogénico inducido por el carcinógeno químico metilcolantreno. En nuestro modelo, el inicio de esta refractariedad coincidió con el comienzo de un estado de inmunosupresión conocido como "eclipse inmunológico" caracterizado por una pérdida o bloqueo de la respuesta inmune antitumoral después que el tumor ha superado cierto tamaño crítico. Este eclipse inmunológico fue acompañado por un proceso de inflamación sistémica en el organismo. El tratamiento de los ratones portadores de tumor con una única dosis del corticoide sintético dexametasona (DX) redujo los parámetros de inflamación sistémica e indujo la reversión del eclipse. Esta reversión no fue por sí misma curativa pero permitió que un tratamiento inmunológico basado en células dendríticas estimuladas con antígenos tumorales, que por sí solo era absolutamente ineficaz, pudiera ejercer un significativo efecto inhibidor sobre un tumor en crecimiento. El esquema de dos pasos que comprende, primero, un tratamiento antiinflamatorio para revertir el eclipse y segundo, una estrategia de vacunación basada en células dendríticas destinada a estimular la respuesta inmune antitumoral, podría servir, eventualmente, como un modelo de inmunoterapia contra tumores en animales y seres humanos.

Although animals can be prophylactically immunized against the growth of tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they become established have been unsuccessful. To understand the nature of this refractoriness we have studied a methylcholanthrene-induced and strongly immunogenic murine fibrosarcoma. In our model, the onset of this refractoriness was associated with the beginning of an immunosuppressive state known as "immunological eclipse" characterized by a loss of the antitumor immune response when tumor grows beyond a critical size. This immunological eclipse was accompanied by the emergence of a systemic inflammatory condition. Treatment of tumor-bearing mice with a single dose of a synthetic corticosteroid, dexamethasone (DX), reduced significantly all parameters of systemic inflammation and simultaneously reversed the immunological eclipse. The reversion of the eclipse upon DX treatment was not curative itself, but allowed an immunological therapy based in dendritic cells pulsed with tumor antigens, which was itself absolutely ineffective, to exert a significant inhibitory effect against an established growing tumor. The two-step schedule using an anti-inflammatory treatment to reverse the immunological eclipse plus a dendritic cell-based vaccination strategy aimed to stimulate the anti-tumor immune response, could serve eventually as a model of immunotherapy against animal and human tumors.

Inhibition of chemically induced carcinogenesis by drugs used in homeopathic medicine.

Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental animals. Presently we have evaluated the inhibitory effects of potentized homeopathic preparations against N'-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in rats as well as 3-methylcholanthrene-induced sarcomas in mice. We have used Ruta, Hydrastis, Lycopodium and Thuja, which are commonly employed in homeopathy for treating cancer. Administration of NDEA in rats resulted in tumor induction in the liver and elevated marker enzymes such as gamma-glutamyl transpeptidase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase in the serum and in liver. Concomitant administration of homeopathic drugs retarded the tumor growth and significantly reduced the elevated marker enzymes level as revealed by morphological, biochemical and histopathological evaluation. Out of the four drugs studied, Ruta 200c showed maximum inhibition of liver tumor development. Ruta 200c and phosphorus 1M were found to reduce the incidence of 3-methylcholanthrene-induced sarcomas and also increase the life span of mice harboring the tumours. These studies demonstrate that homeopathic drugs, at ultra low doses, may be able to decrease tumor induction by carcinogen administration. At present we do not know the mechanisms of action of these drugs useful against carcinogenesis.

Inhibition effect of glycyrrhizin on transplanted mandibular gland fibrosarcoma of mice / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study glycyrrhizin's anticancer effect and its mechanism.</p><p><b>METHODS</b>3-methylcholanthrene were injected into mice's submandibular glands to induce tumor, then transplanted the tumor pieces (1 mm3) to mice. The transplanted tumors were measured, and flow cytometry analysis and cytomorphology observation were conducted.</p><p><b>RESULTS</b>Glycyrrhizin (GL) inhibited the transplanted mandibular gland fibro-sarcoma of mice and the suitable GL dose for inhibiting fibrosarcoma of mice was 1.61 mg per 20 g weight. The GL dose below 3.22 mg per 20 g weight didn't produce remarkable toxicity and side effects. GL induced cytomorphological changes of tumor cells and enhanced immunosuppression of macrophage on fibrosarcoma. The result of flow cytometry showed that tumor cell counts of GL1 and GL2 groups increased remarkably in DNA synthetic prophase, and decreased in DNA synthetic phase.</p><p><b>CONCLUSION</b>GL can inhibit transplanted mandibular gland fibro-sarcoma of mice. The anticancer mechanism of GL may be acting on related enzymes with phagocytosis. The result of flow cytometry showed that the shift of fibrosarcoma cells from G1 phase to S phase was blocked. This suggests that the anticancer action of GL is related to its inhibition of ribonucleotide reductase, a rate-limiting enzyme in DNA synthesis.</p>

Dynamic study on expression of gelatinase A and its natural inhibitor during invasion and metastasis of induced lung cancer in Wistar rats / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression and its relation of gelatinase A (MMP-2), its natural inhibitor (TIMP-2) and DNA index (DI) changes during carcinogenesis, invasion and metastasis in Wistar rats.</p><p><b>METHODS</b>Squamous cell carcinoma of lung was induced with 3-methylcholanthrene (MCA) and diethyinitrosamine (DEN) in iodized oil by left intra-bronchial instillation in 80 Wistar rats. Immrno histochemistay (IHC) and in situ hybridigation were used in the monitor of MMP-2, TIMP-2 proteins and mRNA expression during invasion and metastasis of lung cancer in these rats, DNA index (DI) value was measured by guantitatove image analysis on feulgen stained sections.</p><p><b>RESULTS</b>Along with the carcinogenis, the average poritive MNP-2 and TIMP-2 expressions increased, with positive rates of 8.5% - 85.7% and 6.4% - 35.7%. DI value also underwent the same changes (1.47 +/- 0.54) - (2.87 +/- 0.55). The difference of MMP-2 expression in carcinoma in situ versus early carcinoma and early carcinoma versus metastatic carcinoma are statistically significant (P < 0.05). Companing lung carcinome, the contrel group and non-cancerous lesions, the elevation of MNP-2 and TIMP-2 expressions were also sigmificant (P < 0.01). The DI elevation in carcinoma in situ and dysplasia were obviously significant (P < 0.05). Meanwhile a negative relation was noted in TINP-2 and MMP-2 expressions during carcinogenesis. There was a positive relation between MMP-2 expression and DNA poikiloidy (P < 0.01), which was related to the close relationship between MMP-2 and metastasis in advanced rat lung carcinoma (P < 0.05).</p><p><b>CONCLUSION</b>The excess degradation and disruption of basement membranes by activated MMP-2 may be a key step in inducing lung cancer invasion and metastasis. The imbalance between MMP and TIMP may be a critical factor which affects biologic behavior of lung carcinogenesis, invasion and metastasis.</p>

Expression of inflammation related enzymes during experimental rat lung carcinogenesis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of two inflammation related enzymes - cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) during the experimental rat lung carcinogenesis.</p><p><b>METHODS</b>Eighty Wistar rats were instilled with 3-methylcholanthrene (MCA) and diethylinitrosamine (DEN) into the left lobar branchus to induce lung squamous cell carcinoma. To obtain specimen in every pathological phase during the carcinogenesis, these rats were sacrificed at different intervals. The expression of COX-2 and iNOS in every pathological phase during the carcinogenesis were examined by immunohistochemical method. The immunohistochemical scores (IHS) were calculated by combining an estimate of the percentage of immunoreactive cells with that of the stain intensity.</p><p><b>RESULTS</b>155 specimens of every pathological phase during the carcinogenesis showed: hyperplasia 14, squamous metaplasia 25, dysplasia 33, carcinoma in situ 12, infiltrating carcinoma 54 and metastasis 17. Inflammation and elevated expressions of COX-2 and iNOS were shown in the precancerous lesions. The COX-2 IHS was significantly increased in dysplasia, carcinoma in situ and metastasis (P < 0.01, P < 0.05, P < 0.01 respectively). The iNOS IHS significantly increased in hyperplasia and metastasis (P < 0.05, P < 0.01 respectively). There was a positive correlation between the expression of COX-2 and iNOS (gamma = 0.601 6, P < 0.001).</p><p><b>CONCLUSION</b>COX-2 and iNOS, two inflammation related enzymes, playing important roles in the carcinogenesis of MCA and DEN, induce rat lung squamous cell carcinoma as well as its metastasis. The relation between inflammation and carcinogenesis may partly be explained by the elevated expression of these two enzymes. Nonsteroidal antiinflammatory drug (COX-2 inhibitors) and iNOS inhibitors may possess antitumor activities because of their prevention of bronchial dysplasia, carcinogenesis and metastasis.</p>

Cancare-a herbal formulation inhibits chemically induced tumours in experimental animals.

Cancer chemopreventive potential of Cancare, a multi-herbal formulation on chemically induced tumours was studied by N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats and 20-methylcholanthrene (20-MC) induced sarcoma development in mice. Oral administration of Cancare was found to inhibit the liver tumour development induced by N-nitrosodiethylamine. Animals administered with NDEA had visible liver tumours by the end of 30th weeks and the liver weight was raised to 6.1 +/- 1.4 g/ 100 g body wt. None of the animals treated with Cancare (150 mg/ kg) developed any visible liver tumours by this period and the liver weight was 3.0 +/- 0.6 g/ 100 g body wt. Gamma-Glutamyl transpeptidase, a marker of hepatocellularcarcinoma, which was raised to 83.7 +/- 8. 9 U/l in serum of NDEA treated group was reduced to 35.2 +/- 6.1 U/l by simultaneous administration of Cancare. Elevated levels of serum alkaline phosphatase, glutamate pyruvate transaminase, bilirubin, liver glutathione S-transferase, glutathione and gamma-Glutamyl transpeptidase in the NDEA administered group was significantly reduced by Cancare administration. Cancare administration inhibited the sarcoma development and increased the life span of mice administered with 20-MC dose dependently. All animals in the control group developed sarcomas by 150th day and dead by 174th day after 20-MC administration. Cancare administration (30 mg and 150 mg/kg) inhibited the sarcoma development (46.7 and 60%) as well as increased the life span (53.3 and 66.7%) as estimated on 240th day after 20-MC administration. The results are indicative of the chemopreventive potential of Cancare against chemically induced neoplasmas.

Neovascularisation offers a new perspective to glutamine related therapy.

Angiogenesis or the generation of new blood vessel, is an important factor in the growth of a solid tumor. Hence, it becomes a necessary parameter of any kind of therapeutic study. Glutamine is an essential nutrient of tumor tissue and glutamine related therapy involves clearance of circulatory glutamine by glutaminase. Therefore, using different murine solid tumor models, the present study was undertaken to find out whether the S-180 cell glutaminase has any effect on angiogenesis of solid tumor, or not. Result indicates that the purified S-180 cell glutaminase reduces tumor volume and restrict the generation of neo blood vessels. Therefore, it can be concluded that this enzyme may be an effective device against the cancer metastasis.

Efecto de la carragenina e indometacina sobre el crecimiento de un fibrosarcoma murino / Effect of carrageena and indomethacin on the growth of a murine fibrosarcoma

Los tumores sólidos para crecer más de 2 mm, necesitan desarrollar nuevos vasos sanguíneos. Las células neoplásicas secretan factores de crecimiento que estimulan la angiogénesis y el crecimiento tumoral. La Carragenina bloquea un vitro la unión de los factores de crecimiento a sus receptores. Ensayamos in vivo su acción con el objetivo de analizar si inhibe el desarrollo de un fibrosarcoma murino. Para neutralizar la acción inflamatoria de la Carragenina usamos la Indometacina, que es un antiinflamatorio no esteroide. El tumor usado fue en fibrosarcoma inducido con metilcolanterno en ratones Balb/c y mantenido por pasaje seriado de células tumorales, en ratones de la misma cepa. El volumen de los tumores fue evaluado midiendo dos dimensiones y aplicando la fórmula V = 0.4 x d(2) x D. Los ratones con tumores fueron separados en grupos, uno de los cuales se usó como testigo y los otros tratados en forma separada con indometacina, Carragenina y Carragenina-Indometacina. Se comparó el volumen de los tumores de los ratones tratados con respecto al testigo y el de los tratados entre sí, utilizando el Test t de Student. Se demostró que la Carregenina y la indometacina, inhiben el desarrollo del fibrosarcoma. La acción inhibitoria de la Carragenina sobre el crecimiento tumoral es significativamente mayor que el efecto antitumoral de la Indometacina y el de la Corragenina-Indometacina.

Antioxidant and anticarcinogenic activity of Lycovin--an indigenous herbal preparation.

Aqueous extract of Lycovin has been found to be a potent inhibitor of lipid peroxide formation, (IC50 = 500 micrograms/ml) and scavenger of hydroxyl radical (IC50 = 44 micrograms/ml) and superoxide radical (IC50 = 30 micrograms/ml) in vitro. Lycovin syrup 1.5 ml and 7.5 ml/kg body wt administered orally, reduced the development of sarcoma induced by 20 MC by 35% and 70% respectively. Lycovin syrup was also found to inhibit the hepatocarcinogenesis induced by NDEA. The tumour incidence was 100% in the control group, while none of the drug treated animals developed tumour. Liver weight, gamma-glutamyl transpeptidase (GGT), GSH-S-transferase (GST), reduced glutathione, (GSH) and aniline-4-hydroxylase in liver were elevated in NDEA alone treated animals. The serum parameters indicative of liver injury such as bilirubin, lipid peroxides, alkaline phosphatase and glutamate pyruvate transaminase were also elevated by NDEA administration. These elevated parameters were significantly reduced in animals treated with Lycovin syrup along with NDEA in a dose dependent manner. Even though the exact mechanism of action is not known at present, the observed anticarcinogenic activity may be due to the inhibition of P.450 enzyme activity and subsequent inhibition of the production of the ultimate carcinogen as well as scavenging of oxygen free radicals during promotion of the transformed cell.

The Effect of All-Trans-Retinoic Acid on the Activity and the Gene Expression of Drug Metabolizing Enzymes in Rat Skin / 대한피부과학회지

BACKGROUND: The activity of drug metabolizing enzymes and the modulation of their expression by inducers in the skin are the key factors for understanding of pharmacological and toxic effects of topically applied drugs. The role of these enzymes is of major importance, as they may contribute to determine the steady-state levels of biologically active substances. 3-Methylcholanthrene and all-trans- retinoic acid have been known to be inducers of the drug metabolizing enzymes. And all-trans- retinoic acid has many biological actions including anti-cancer effects. OBJECTIVE: The purpose of this study was to evaluate the effect of all-trans-retinoic acid on inducing the expression and modulation of genetic polymorphism of drug metabolizing enzymes as well as to estimate the role of all-trans-retinoic acid in carcinogenesis and drug interactions. METHODS: We analyzed the activities of CYP1A1(Cytochrome P450 1Al), NADPH cytochrome P450-reductase, UGT1 and GST after administration of 3-methylcholanthrene and all-trans-retinoic acid to the Sprague-Dawley male rats. We observed the inducible gene expression of CYP1A1, UGT1, GSTJt by RT-PCR and the genetic polymorphism of CYP1A1, UGT1, GSTK by PCR. RESULTS: 1. The expression of CYP1A1, NADPH cytochrome P450-reductase, UGT1 and GST was induced by 3-methylcholanthrene and all-trans-retinoic acid. That of NADPH cytochrome P450-reductase and UGT1 is pronouncedly enhanced by all-trans- retinoic acid. 2. The effects of 3-methylcholanthrene and all-trans-retinoic acid on inducing the expression of CYP1A1 and UGT1 correlated with an increase of mRNA expression levels of CYP1A1 and UGT1. The modulation of mRNA expression levels of GST was downregulated by all-trans-retinoic acid. 3. The genetic polymorphism of CYP1A1 was induced by 3-methylcholanthrene and all-trans- retinoic acid, and that of GSTM1 was not affected by the inducers. The induction of genetic polymorphism of GST was down regulated by all-trans-retinoic acid. CONCLUSION: 3-Methylcholanthrene and all-trans-retinoic acid modulate the inducible expression and genetic polymorphism of drug metabolizing enzymes differentially. All-trans-retinoic acid can modulate the metabolism of procarcinogen such as 3-methylcholanthrene by inducing drug metabolizing enzymes. Furthermore, the elucidation of the molecular mechanisms underlying the regulation of drug metabolizing enzymes by 3-methylcholanthrene, all-trans-retinoic acid and other drugs could help to understand their respective roles in drug interactions and carcinogenesis.

EFFECTS OF PROPOLIS ON THE TUMORIGENESIS AND THE GROWTH OF SPLENOCYTES AND MACROPHAGES IN MICE

The propolis, honey bee hive product, is a folk medicine for treating various ailments. Many important pharmaceutical properties have been ascribed to propolis, including anti-inflammatory, antimicrobial, immunormodulatory and carcinostatic activities. The purpose of this study was to examine the effects of ethanol extracted propolis(EEP) on the tumorigenesis and the growth of splenocytes and macrophages in ICR mice. Topical application of 0.2, 2 or mg/ml of EEP on the back of each mice 30 minutes before the application of 7, 12-dimethylbenz (a)anthracene(DMBA) and 12-O-tetradecanoylphorbol-13-acetate(TPA) inhibited the number of tumors per mouse by 61, 75 or 100%, respectively, and tumor size per mouse was decreased by 37, 75 or 100%, respectively. In 3-methylcholanthrene induced tumorigenesis, topical application of same doses of EEP inhibited the number of tumors per mouse by 19, 60 or 90%, and the tumor size per mouse by 58, 85 or 98%, respectively. Oral administration of mice with EEP at 0.2mg or more per day per mouse for 28days increased pulmonary metastases of the B16F10 melanoma cells in ICR mice by 240%, EEP of 3.75ug/ml or more inhibited the growth of ICR mouse spleen cells significantly(p<0.05), but EEP 0.94ug/ml or less did not affects the growth of the spleen cells in vitro. Caffeic acid phenethyl ester(CAPE), which is derived from the propolis, of 0.94ug/ml or less increased the growth of spleen cells, but at the concentations of 3.75ug/ml or more, decreased the growth of spleen cells. EEP of 3.75-15ug/ml increased the growth of mouse peritoneal macrophages, but at the concentration of 60ug/ml, decreased the growth of the macrophages significantly(p<0.01). And also, CAPE of 0.94ug/ml or less did not affects the growth of the macrophages, but at the concentrations of 3.75ug/ml or more, decreased the growth of the macrophages significantly(p<0.01). DDP or CAPE inhibited the nitric oxide production of mouse peritoneal macrophages in concentration-dependent manner regardless of the number of the macrophages in vitro. These results suggest the possibility that the EEP or CAPE might suppress the immune function by the inhibition of growth and activity of spleen cells and macrophages.

Effect of inducers on hepatic microsomal mixed function oxidase system of male rats during food restriction.

Phenobarbital (PB; 80 mg/kg, ip) or 3-methylcholantrene (3-MC; 20 mg/kg, ip) was administered to Wistar male rats at the end of the feeding period of 30 days and the effects of food restriction (FR) and FR followed by inducer treatment on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH dependent lipid peroxidation and glutathione-s-transferase activities were studied. In both, PB and 3-MC treatment, the magnitude of increase in microsomal protein content, cytochrome b5 and aminopyrine N-demethylase (APND) activity was less in FR animals than in ad libitum fed; while cytochrome P-450 levels and activities of cytochrome c reductase and acetanilide hydroxylase (ACOH) were higher in FR animals. NADPH dependent lipid peroxidation and cytosolic glutathione-s-transferase activity were also enhanced due to PB and 3-MC treatment but the magnitude of increase was less in FR animals. The ACOH activity increased to a greater extent than APND activity in FR animals following PB and 3-MC treatment. It is suggested that the response to inducers in the FR animals differ from that in the ad libitum fed rats.

Adult gerbil epidermal cells resistant to terminal differentiation associated with initiation of carcinogenesis

In order to identify the cellular basis of the gerbil skin unresponsiveness to two-stage carcinogenesis, it was studied the effect of an initiating dose of carcinogen on the biological behaviour of gerbil skin. Treatment of adult gerbil epidermal cells either in vivo or in vitro with 3-methylcholanthrene yielded cells which were resistant to terminal differentiation induced by calcium. These results support the concept derived from the mouse model system of skin carcinogenesis in which initiation is associated with an altered program of epidermal differentiation. The results also suggest that relative resistance of gerbil skin to two-stage carcinogenesis is related to promotion stage

Comparison between the effects of early schistosoma mansoni infection and the classical inducers phenobarbitone and 3-methylcholanthrene on some hepatic microsomal monooxygenases

Hepatic schistosomiasis was induced experimentally in male albino mice using Schistosoma mansoni [S. Mansoni] cercariae for a period of 33-days post infection. Five different levels of infection [60, 120, 180, 300 and 600 cercariae/mouse] were used for the assessment of the comparison of their effects on some hepatic microsomal monooxygenases with those produced by classical enzyme inducers phenobarbitone [PB] and 3-methylcholanthrene [MC]. Similar to the two tested classical inducers, the 33 days post infection of mice with S. mansoni increased the total microsomal protein content [23.6%, 40.5%, 59.9%, 47.2% and 33.7%] and the specific concentration of cytochrome P450 Cyt P450 [26.8%, 35.4%, 71.7%, 56.7% and 48.0%] at all tested infection levels. The maximum increase was recorded at the infection level of 180 cercariae/mouse

Tumores provocados por metilcolantreno y lapachol. Seguimiento del desarrollo mediante citología / Tumors caused by methylcholanthrene and lapachol. Follow-up of desenvolviment by cytology

El presente trabajo fue realizado con el objetivo de estudiar el efecto por el lapachol (LAP) al ser administrado a rats en forma simultánea con un carcinógeno químico, el 20-merilcolantreno (MCA). Los animales fueron divididos en 4 lotes: A-Lote tratado con 80 mg de MCA (n=11 animales), B-Lote tratado con 80 mg de MCA+LAP 100 mg/Kg peso/día (n=15 animales), C-Lote tratado con LAP 100 mg/Kg peso día (n=12 animales), D-Lote control sin tratamiento (n=13 anisales). Los estudios citológicos así como la aplicación de técnicas citoquímicas permitieron conocer el diagnóstico de benegnidad o malignidad apenas producida la aparición del tumor. Estudios histopatológicos posteriores confiraaron la aparición el el 53 por ciento de los animales del lote B de tumores compatibles con adenocarcinomas pobremente diferenciados de glándula salival y en el 18.2 por ciento (2/11) de los animales del lote A de fibroadenomas de la glándula mamaria. Asimismo fue observada la presencia de uno o varios nódulos suprahepáticos en vencidad al ligamento suspensorio e histológicamente definidos como de hiperplasia nodular en el 33 por ciento (4/12) de los animales del lote C y en 13.3 por ciento (2/15) del B no produciéndose desarrollo de dichos nódulos en los lotes A y D. En el riñón fue observada dilatación quística de los túbulos en el 60 por ciento (9/15) y 83.3 por ciento (10/12) de los animales del lote B y C respectivamente. A partir del tumor primitivo de glándula salival fue desarrollada uma linea de tumores transplantables cuyo seguimiento fue realizado citológicamente. Se reafirma la importancia del diagnostico citológico e histopatológico para el estudio del efecto farmacológico de drogas que como el Lapachol son empleadas como antitumorales sin conocerse sus efectos nocivos.

3 Metilcolantreno (3MC): inducción de fibrosarcomas y de carcinomas escamosos en el ratón mus musculus

El 3 metilcolantreno es un carcinogeno pluripotente. el autor ha logrado inducir en el ratón Mus musculus, fibrosarcomas y carcinomas epidermoides por inoculación subcutánea en el primer caso y por escarificación de la piel, en el segundo caso. El porcentaje de fibrosarcomas es alto (90 por ciento), mientras que en el caso de carcinomas escamosas es bajo (9 por ciento). Se considera al ratón Mus musculus como modelo experimental, a pesar de ser una estirpe no significa, pues los fibrosarcomas crecen progresiva y uniformemente, como si se trata de animales singénicos. Este patron de crecimiento servirá para ensayos experimentales, terapéuticos sobre todo. Se obtienen además datos curiosos (cambio de color de ojos, pigmentación e hiperrofia de glándulas mamarias y retardo de crecimiento corporal de algunos animales) que podrían despertar el ánimo del investigador en orden a esclarecer los fenómenos biológicos involucrados.

Efeito de promotores tumorais em pele de gerbil, Meriones unguiculatus / Tumor promoters effect in gerbil skin, Meriones unguiculatus

Supondo que a resistência relativa da pele de gerbil adulto à carcinogênese química estaria relacionada a um fenômeno de adaptaçäo ao processo de promoçäo tumoral, foi caracterizado o efeito de óleo de cróton (OC) e peróxido de benzoíla (PB) sobre a pele de gerbil, através do estudo das alteraçös morfológicas, correlatas à atividade promotora e induzidas em funçäo da dose administrada, da frequência do tratamento e da associaçäo ao iniciador metilcolantreno (MC) em modelos bifásicos e trifásicos de carcinogênese. Verificou-se que uma única aplicaçäo tópica de OC (0,94 mg e 1,88 mg) ou PB (20 mg e 40 mg) induz, na epiderme interfolicular, grau similar de hiperceratose e hiperplasia dose-dependente; outros efeitos, como espessamento da epiderme, hipertrofia celular e inflamaçäo, eram mais acentuados pelo tratamento com OC. O efeito hiperplásico, também mais acentuado com OC, decorreria do estímulo proliferativo e do desiquilíbrio entre proliferaçäo e diferenciaçäo epidérmica...

Fibrosarcomas inducidos por metilcolantreno (MC) tratado con el conjugado proteina C reactiva acido fólico en liposomas

La unión química covalente de la Proteina C Reactiva con el Acido Fólico forma una nueva molécula, un inmunógeno peculiar proteínico-hapténico , el mismo que es transportado al torrente circulatorio por liposomas (vesiculas fosfolípidas). Este modelo terapéutico especial y original, sería capaz de inhibir el crecimiento tumoral ocasionado por una respuesta antigénica y potencializada.