Ehrlich Tumor Research Articles

44. Cohabitation with a sick-cage mate exacerbates allergic lung inflammatory response in mice

The objective of this study was analyze the effects of cohabitation with sick partner on allergic lung inflammatory response in ovalbumin (OVA) sensitized and challenged mice. Pairs of mice were divided into control and experimental groups. Within each group, one mouse from each pairs was immunized with a solution containing (OVA). The remaining mouse from the experimental group was injected with Ehrlich tumor cells being designated as “companion of sick partner” (CSP); the remaining mouse of the control group was injected with PBS being designated as “companion of healthy partner” (CHP). CSP mice presented in relation to CHP mice: increased number of eosinophils and neutrophils in the BAL; increased IL-4 and IL-5 levels and decreased IL-10 and INF-γ in the BAL supernatant; increased IgG1-OVA and decrease IgG2a-OVA levels on peripheral blood; increased expression of L-selectin in the BAL granulocytes; decreased in vitro tracheal reactivity to metacholine; no changes on plasma corticosterone levels and increased levels of plasmatic noradrenaline. The results suggest that the exacerbation of the allergic lung inflammatory response in CSP mice is a consequence of the psychological stress induced by forced long-term cohabitation with sick the partner, a fact that might ultimately depend on the changes induced by catecholamines on Th1/Th2 balance, toward a Th2 cytokine profile and finally the recruitment and activation of eosinophils in the airways. FAPESP: 2012/03372-3; 2009/51886-3.

Neuroimmune Interactions and Psychologycal Stress Induced by Cohabitation with a Sick Partner: A Review

This study reviews the neuroimmunological consequences elicited in mice from long-term cohabitation with tumor-bearing conspecifics. Two types of experiments were performed; one used Swiss female mice and Ehrlich tumor cells, and the other used C57Bl/6 female mice and B16F10 melanoma cells. The female Swiss mice and the C57Bl/6 mice were divided into two groups, i.e., control and experimental. One mouse in each control pair was treated with control solutions (1.0 mL/kg); the other was kept undisturbed and called the 'companion of health partner' (CHP). One mouse in each experimental pair was inoculated with 5 x 10(6) Ehrlich tumor cells or with 10(6) murine B16-F10 melanoma cells; the other mouse, which was the subject of the performed studies, was left undisturbed and called the 'companion of sick partner' (CSP). Although we used two different strains of mice and two different tumor types, the CSP mice presented, in relation to the CHP mice, an increased locomotion in the open field and plus maze apparatuses and no changes in the corticosterone serum levels before and after the immobilization-stress challenge. The Swiss CSP mice showed a reduced level and an increased turnover rate of hypothalamic noradrenaline (NE), as well as increased plasmatic levels of adrenaline and NE. Changes in the immune cell phenotype and activity were also observed in the Swiss and C57Bl/6 CSP mice. The study found that odor cues left by the Ehrlich tumor-injected Swiss mice are aversive and may therefore be responsible for the neuroimmune changes reported in the CSP mice. It is proposed that the final neural link between the neuroimmunological changes observed in the CSP mice involves psychogenic stress imposed by the housing condition and the activation of the brain catecholaminergic pathways and the sympathetic nervous systems.

Dual effects of indoleamine 2,3-dioxygenase inhibitors on the therapeutic effects of cyclophosphamide and cycloplatam on Ehrlich ascites tumor in mice.

Ethyl pyruvate, an inhibitor of indoleamine 2,3-dioxygenase, slightly suppressed the growth of transplantable Ehrlich tumor in mice and significantly potentiated the therapeutic effect of cyclophosphamide. Another inhibitor amidoxime produced a similar effect. However, both ethyl pyruvate and amidoxime significantly reduced the effect of cycloplatam therapy. The observed changes can be stipulated by different effects of cyclophosphamide and cycloplatam on the subpopulations of lymphoid cells taking part in the formation of antitumor immunity and resistance to tumors.

Ehrlich tumor inhibition using doxorubicin containing liposomes

Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm3) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

Biochemical analysis and antitumour effect of Abrus precatorius agglutinin derived peptides in Ehrlich's ascites and B16 melanoma mice tumour model

Anticancer and immunostimulatory properties of tryptic digest peptides of Abrus precatorius agglutinin protein (10kDAGP) have already been reported. Here attempt has been made to further validate anticancer properties of 10kDAGP peptides in Ehrlich's ascites carcinoma (EAC) and B16 melanoma (B16M) bearing mice models and to analyze 10kDAGP by anion exchange chromatography and RP-HPLC for obtaining the bioactive fraction from the total peptide pool. 10kDAGP treatment decreased the tumour pack volume by ∼82% for EAC and 58.8% for B16M. It also showed increase in ex vivo proliferation of splenocyte and thymocyte isolated from tumour bearing mice and increase in TNF-α and Interferon-γ in splenocyte culture supernatant. From chromatographic analysis it was found that anionic peptide fraction may be responsible for anti-proliferative activities of 10kDAGP. As most anticancer peptides are cationic in nature, further studies regarding bioactivity of anionic peptide fraction may lead to novel anticancer peptides and pathways of action.

Cohabitation with a sick partner increases allergic lung inflammatory response in mice.

The bidirectional relationship between the nervous system and the immune system is relevant for homeostatic organism maintenance. Studies from our laboratory showed that 14days of cohabitation with a sick partner (injected with Ehrlich tumor cells-TAE) produced behavioral, neurochemical, endocrinological and immunological changes. This study analyzes the effects of cohabitation with an Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory response in mice. Pairs of male mice were divided into three groups: naïve, control and experimental. Animals of the naïve group were kept undisturbed being used for the assessment of basal parameters. One animal of each experimental and control pair of mice was immunized with OVA. On ED(0), these OVA-immunized animals received an OVA booster. At this day (D(0)) the experimental mice that were kept undisturbed were inoculated with 5×10(6) Ehrlich tumor cells; their immunized cage-mates were then referred as to CSP ("companion of sick partner"). The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9% NaCl; their sensitized cage-mates were subsequently referred as CHP ("companion of health partner"). The OVA challenge was performed on CSP and CHP mice on ED(12) and ED(13); blood and tissue collection were performed on ED(14). Fourteen days after cohabitation, in comparison to the CHP mice, the CSP mice displayed the following: (1) an increased number of eosinophils and neutrophils in the BAL, (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and decreased levels of IL-10 and IFN-γ in the BAL supernatant, (5) increased levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific IgE in the peripheral blood, (6) increased expression of L-selectin in the BAL granulocytes, (7) decreased tracheal reactivity to methacholine measured in vitro, (8) no changes in plasma corticosterone levels and (9) increased levels of plasmatic noradrenaline. These results suggest that allergic lung inflammatory response exacerbation in CSP mice is a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system (SNS) through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal's airways.

Viscum album L. influence on the antioxidant enzymes activity in ehrlich tumor cells in vivo.

Viscum album L., (Santalaceae) is a semi-parasitic plant that grows on various trees. It is widely used in cancer treatment. The present study assesses the influence of oxidative stress in mistletoe induced tumor cytotoxicity in tumor cells. Ehrlich ascites carcinoma (EAC) was induced by injecting 106 cells/animal, ip, (in day 0), in Swiss female mice. Mistletoe ethanolic extract was injected in dose of 50 mg/kg b.w, i.p., three times before (days -6, -3, -1) and after (1, 3, 6) EAC inoculation. 14 days after EAC inoculation, the mice were euthanized for estimation of tumor proliferation, hematological parameters, the antioxidant status in plasma and tumor cells. In EAC bearing mice, Viscum album ethanolic extract exhibited a significant antiproliferative effect, as compared with untreated group, reflected in reduced EAC cell concentration, increased percentage of non-viable cells and low plasma antioxidant activity. These changes were found only in pre-treated groups, while post-treated groups showed no significant differences. The antiproliferative effect was significantly correlated with decreased activity of plasma antioxidant enzymes. In pre-treated groups, antioxidant enzymes activity of the EAC tumor cells experienced important changes, in correlation to cytotoxic effect, whereas less significant variations in post-treated group were found. Even if the underlying mechanisms are still to be ascertained, Viscum album alcoholic extract proved, a significant, selective antitumor effect, without obvious harmful effect on mice.

Antitumor activity of Pleurotus ostreatus polysaccharide fractions on Ehrlich tumor and Sarcoma 180

The medicinal properties of fungi of the genus Pleurotus have attracted great interest due to their therapeutic properties. Polysaccharides synthesized by Pleurotus, including the β-glucans are considered the main responsible for its therapeutic properties. This study aimed to evaluate the efficacy of polysaccharidic fractions extracted from mycelial biomass of Pleurotus ostreatus DSM 1833 in inhibiting the development of Ehrlich Tumor (ET) and Sarcoma 180 (S-180). FC, FI and FII fractions provided 60.6, 76.5 and 73.6% of ET inhibition, respectively (mean value of about 70%) while FS, FIII-1 and FIII-2 showed no inhibition against ET. FII and FIII-2 resulted in 85.6 and 93.6% (mean value of about 90%) while FIII-1, FC and FS resulted in 54.1 and 0%, respectively, of S-180 inhibition. The yields of the fractions FS, FI, FII, FIII-1 and FIII-2 obtained from P. ostreatus mycelial biomass were 11.6, 1.3, 0.4, 0.65 and 0.35%, respectively. FII fraction (30mg/kg) apparently had no toxic effect on healthy animals, since no difference between the body weights of animals in substance control (SC) and negative control (NC) groups was observed.

Odor Cues Released by Ehrlich Tumor-Bearing Mice Are Aversive and Induce Psychological Stress

Background/Aims: This study aimed to verify if odor cues released by Ehrlich tumor-bearing mice are aversive and stressful. Methods: Female mice were divided into a control group and an experimental group. One animal of each experimental pair of mice was inoculated with 5 × 10⁶ Ehrlich tumor cells intraperitoneally; the other animal was kept undisturbed and was referred to as a CSP (companion of sick partner). One mouse of each control pair was treated intraperitoneally with 0.9% NaCl (1 mg/kg); the other animal (CHP, companion of healthy partner) was kept undisturbed. Results: It was shown that, in relation to CHP, CSP mice (1) spent less time within the companion zone in a T-maze place preference test, (2) had increased levels of social interaction, (3) had increased levels of plasmatic adrenaline and noradrenaline and (4) displayed no changes in serum corticosterone levels before and after an immobilization stress challenge. It was also shown that (5) cohabitation with 2 tumor-bearing mice was more effective in decreasing neutrophil oxidative burst than cohabitation with 1 sick partner and (6) the presence of a healthy conspecific within the cage of the tumor-injected/CSP pair abrogated the effects of cohabitation on neutrophil activity. These results show that odor cues released by Ehrlich tumor-injected mice are aversive and induce psychological stress. Conclusion: We postulate that the aversive response induced by the chemosignals released by Ehrlich tumor-injected animals activates the sympathetic nervous system and causes the neuroimmunal changes that occur in the mice cohabiting with the sick mice.

English

Omega-3 essential fatty acids (ω-3 FATs); found in the highest concentrations in fish oil, claim a plethora of health benefits. The present study aims to evaluate the biological effects of ω-3 FATs supplementation against Ehrlich carcinoma (EC) induced inflammation, oxidative stress, biochemical and histopathological alterations in the liver tissue of albino mouse. ω-3 FATs were orally administered via gavage to mice for a period of 30 consecutive days at a dose of 300 mg/kg body weight. On the 7th day of ω-3 FATs administration, female mice were subcutaneously injected with 0.2 ml of Ehrlich ascite carcinoma for solid tumor induction. The present study revealed that, subcutaneous injection of Ehrlich solid tumor led to hepatic oxidative stress (as significant increase in lipid peroxidation (thiobarbituric acid reactive species, TBARS), concomitant with a significant decrease in glutathione and antioxidant enzymes), systemic inflammation (significant increases in C-reactive protein, tumor necrosis factor-alpha and leukocyte counts) and biochemical alterations (as increase in liver function enzymes)). While in the tumor tissue, significant increase in tumor TBARS content and non significant changes in glutathione and antioxidant enzymes were observed. Histopathological studies showed that EC cells metastasis caused fatty degeneration, enlargement of liver cells nuclei and presence of necrosis. Pretreatment of animals with ω-3 FATs significantly reduced tumor size and markedly improved most of the biochemical parameters associated with the inoculation of EC. It could be concluded that ω-3 FATs administrated to mice, reduce tumor size, inhibit systemic inflammation, improving liver function profile, modulating lipid peroxidation and augmenting antioxidant defense system in EC bearing mice.   Key words: Ehrlich carcinoma (EC), omega-3 fatty acids, liver.

Higher Insulin Sensitivity and Impaired Insulin Secretion in Cachetic Solid Ehrlich Tumour-Bearing Mice

Insulin secretion is mainly regulated by blood glucose concentration. On the other hand, changes in peripheral insulin sensitivity induce compensatory adaptations in pancreatic β-cells to maintain normoglycaemia. Tumour presence causes dramatic alterations in glucose homeostasis and insulin secretion because of the high glucose consumption by the tumour cells. Here, we investigated insulin secretion in solid Ehrlich tumour-bearing mice in association with cachexia. For that, male adult Swiss mice were subcutaneously inoculated with solid Ehrlich tumour cells and sacrificed at 14 days after tumour implantation (SET), while control mice received saline alone (CTL). Insulin secretion, following different stimuli, glucose tolerance, and insulin sensitivity as well as the expression of key proteins involved in insulin secretion was assessed. The SET group showed decreased glycaemia, insulinaemia, hepatic glycogen and body weight, and increased plasma free fatty acids and triglycerides, characteristics of cancer cachexia. A very interesting finding in this study was the development of higher glucose tolerance and insulin sensitivity in SET group. The dose-response curve of insulin secretion to increasing glucose concentrations (2.8-22.2 mM) showed an EC50 of 10 mM glucose for CTL mice and 13 mM glucose for SET mice. Insulin secretion was significantly reduced in SET islets at 30 mM KCl, 100 μM carbachol, 20 mM arginine, and 20 mM leucine. Moreover, AKT, PKA, PKC, and AchRM3 expressions were reduced by 17% to 24% in SET animals. These results, mainly the augmented insulin sensitivity, show that SET is an interesting model to study alterations in pancreatic function and carbohydrate metabolism in cancer cachexia.

Nerve growth factor from cobra venom inhibits the growth of Ehrlich tumor in mice.

The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved.

Evaluation of the effects of methotrexate released from polymeric implants in solid Ehrlich tumor

In this study, the effects of the controlled and sustained release of methotrexate from poly(ɛ-caprolactone) implants were evaluated in the solid Ehrlich tumor. The drug locally leached from the implantable devices was capable of reducing the tumor growth and the necrotic areas of the tumor site. Furthermore, the methotrexate exerted its anti-tumor effect probably by the recruitment of neutrophils at the tumor site, which assisted in modulating the growth of the tumor. The polymeric implants containing methotrexate could be a chemotherapic alternative to treat locally solid tumors with lower systemic side effects.

B-1 cells and concomitant immunity in Ehrlich tumour progression

Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells’ participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth.

Long-Term Treatment with Aqueous Garlic and/or Tomato Suspensions Decreases Ehrlich Ascites Tumors.

We evaluated the preventive and therapeutic effects of aqueous suspensions of garlic, tomato, and garlic + tomato in the development of experimental Ehrlich tumors in mice. The aqueous suspensions (2%) were administered over a short term for 30 days before tumor inoculation and 12 days afterward, and suspensions at 6% were administered for 180 days before inoculation and for 12 days afterward. The volume, number, and characteristics of the tumor cells and AgNOR counts were determined to compare the different treatments. Aqueous 6% suspensions of garlic, tomato, and garlic + tomato given over the long term significantly reduced tumor growth but when given over the short term, they did not alter tumor growth.

Histopathological evaluation of tumor necrosis and volume after cyanogenic chemotherapy.

To determine the percentage of tumoral necrosis and volume after cyanogenic chemotherapy. Histopathological findings of 20 Swiss mice inoculated subcutaneously in the left abdominal wall with 0.05 ml of cell suspension containing 2.5 x 10(5) viable cells of the Ehrlich tumor were evaluated. The tumor response to cyanogenic chemotherapy was determined using a system that comprises two inhibition factors of tumor growth by calculating the percentage of necrosis in the tumor tissue and calculation of tumor volume in treated animals relative to that in control animals. The importance of this system has been validated by the correlation between tumor inhibition in the groups treated with the respective percentages of necrosis. While the control group presented an average of 13.48 ± 14.71% necrosis and average tumor volume of 16.18 ± 10.94, the treated group had an average of 42.02 ± 11.58 and 6.8 ± 3.57, respectively. The tumor inhibition was significantly associated with treatment (p=0.0189). The analysis of necrosis percentage showed a significant prognostic importance (p=0.0001). It is concluded that the effect of cyanogenic chemotherapy showed strong inhibitory action of tumor growth, as well as an increase in its area of necrosis.

Antitumor activity of photodynamic therapy performed with nanospheres containing zinc-phthalocyanine

BackgroundThe increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments. Among these, photodynamic therapy (PDT) has been proposed as a very promising new modality in cancer treatment with the lowest rates of side effects, revealing itself to be particularly successful when the photosensitizer is associated with nanoscaled carriers. This study aimed to design and develop a new formulation based on albumin nanospheres containing zinc-phthalocyanine tetrasulfonate (ZnPcS4-AN) for use in the PDT protocol and to investigate its antitumor activity in Swiss albino mice using the Ehrlich solid tumor as an experimental model for breast cancer.MethodsEhrlich tumor’s volume, histopathology and morphometry were used to assess the efficacy of intratumoral injection of ZnPcS4-AN in containing tumor aggressiveness and promoting its regression, while the toxicity of possible treatments was assessed by animal weight, morphological analysis of the liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. In order to evaluate the efficacy of PDT, groups of animals treated with intratumoral injection of doxorubicin (Dox) were also investigated.ResultsIntratumoral injection of ZnPcS4-AN was found to be efficient in mediating PDT to refrain tumor aggressiveness and to induce its regression. Although tumor volume reduction was not significant, PDT induced a remarkable increase in the necrosis area seen in the tumor’s central region, as in other experimental groups, including tumor and Dox treated groups, but also in the tumor’s peripheral region. Further, PDT showed minimal adverse effects. Indeed, the use of ZnPcS4-AN in mediating PDT revealed anti-neoplastic activity similar to that obtained while using intratumoral Dox therapy.ConclusionsPDT mediated by the new formulation ZnPcS4-AN enhanced the inhibition of tumor growth while producing practically no adverse effects and thus emerges as a very promising nanotechnology-based strategy for solid cancer treatment.

Tissue Distribution and Efficacy of Gold Nanorods Coupled with Laser Induced Photoplasmonic Therapy in Ehrlich Carcinoma Solid Tumor Model

Gold nanorods (GNR) within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.

Sulfane sulfur deficiency in malignant cells, increasing the inhibiting action of acetone cyanohydrin in tumor growth

To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. Thirty male Swiss mice were inoculated with 1 x 10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 μg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.

84. Cohabiting with a sick mate: Relevance of olfactory contact to innate immune activity

Cohabitation with a sick cage-mate induced behavioral and immunological changes. Divergent signals including visual, olfactory, chemical, or tactile (Communication cues = CC) have been described as being involved in communication among individuals of the same and different species. This work was designed to analyze the effects of different CC on neutrophil activity (oxidative burst and phagocytosis). Female mice were paired and divided into one control (C) and one experimental (E) group. One mice of each E pair was inoculated i.p. with 5 X 106 Ehrlich tumor cells; the other animal of the pair, the object of this study, was not treated being referred to as “companion of sick partner” (CSP). One mouse of each C pair was called “companion of health partner” (CHP) remaining undisturbed; the other was injected with NaCl 0.9% (0.1 ml/10 g). Three experiments were done to analyze the effects of physical contact, olfactory and visual cues on neutrophil activity. Experimental mice were analyzed after fourteen days of cohabitation. Results showed that physical contact and visual cues were not relevant for neutrophil activity changes observed after cohabitation. On the contrary, the olfactory cures were fundamental for the decrease in neutrophil oxidative burst and phagocytosis. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the immune changes reported for cohabitation with a sick companion.