Yacon (Smallanthus sonchifolius) and Lactobacillus acidophilus CRL 1014 reduce the early phases of colon carcinogenesis in male Wistar rats

The modifying effects of aqueous yacon extract (AYE) and Lactobacillus acidophilus CRL 1014 against colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats were investigated. Animals were allocated into five groups: G1: untreated group; G2: DMH-treated group; G3: DMH + L. acidophilus-treated group; G4: DMH + AYE-treated group; G5: DMH + L. acidophilus and AYE-treated group. A significant reduction (p < 0.05) in leukocyte DNA damage and in colonic cell proliferation was observed after the first DMH administration in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. In this moment, a significant increase (p < 0.05) in colonic apoptosis was also observed in G3 (probiotic) and G5 (synbiotic) groups. In special, at five months after DMH administrations, a significant reduction (p < 0.05) in ACF development was observed in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. Incidence of colon tumors was lower at five months in G4 (prebiotic) and G5 (synbiotic) groups but not in eight months after DMH administrations. In conclusion, the findings suggest that the oral treatments have potential effects as a chemopreventive agent against colon carcinogenesis on an early stage of tumor development.

High-fat diet causes an imbalance in the colonic serotonergic system promoting adipose tissue enlargement and dysplasia in rats

A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of viscera! adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Early stages of experimental colon carcinogenesis inhibit mast cell-dependent mucosal immune function of the distal colon

Inhibition of local host immune reactions is one mechanism contributing to tumor progression. To determine if alterations in local immune functioning occur during colon carcinogenesis, a model mucosal immune response, type I hypersensitivity against the intestinal parasite Trichinella spiralis, was first characterized in normal mice and then examined during experimental colon carcinogenesis. Segments of sensitized colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current ($\rm\Delta I\sb{sc}$) that was antigen-specific and inhibited by furosemide, implicating epithelial Cl$\sp-$ secretion as the ionic mechanism. The immune-regulated Cl$\sp-$ secretion by colonic epithelial cells required the presence of mast cells with surface IgE. Inhibition of potential anaphylactic mediators with various pharmacological agents in vitro implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced $\rm\Delta I\sb{sc}$, with 5-hydroxytryptamine also playing a role. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 wk had a decreased response to antigen, confirming the major role of prostaglandins in generating the colonic I$\sb{\rm sc}$. To determine the effects of early stages of colon carcinogenesis on this mucosal immune response, mice were immunized with T. spiralis 1 day after or 8 wk prior to the first of 6 weekly injections of the procarcinogen 1,2-dimethylhydrazine (DMH). Responsiveness to antigenic challenge was suppressed in the distal colon 4-6 wk after the final injection of DMH. One injection of DMH was not sufficient to inhibit antigen responsiveness. The colonic epithelium remained sensitive to direct stimulation by exogenous Cl$\sp-$ secretagogues. Decreased antigen-induced $\rm\Delta I\sb{sc}$ in the distal colon was not due to systemic immune suppression by DMH, as the proximal colon and jejunum maintained responsiveness to antigen. Also, rejection of a secondary T. spiralis infection from the small intestine was not altered. Tumors eventually developed 25-30 wk after the final injection of DMH only in the distal portions of the colon. These results suggest that early stages of DMH-induced colon carcinogenesis manipulate the microenvironment such that mucosal immune function, as measured by immune-regulated Cl$\sp-$ secretion, is suppressed in the distal colon, but not in other regions of the gut. Future elucidation of the mechanisms by which this localized inhibition of immune-mediated ion transport occurs may provide possible clues to the microenvironmental changes necessary for tumor progression in the distal colon. ^

Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different from the genes known to be somatically mutated in colon cancer.

The predisposition to colon cancer is multigenetically controlled in animals and probably also in humans. We have analyzed the multigenic control of susceptibility to 1,2-dimethylhydrazine-induced colon tumors in mice by using a set of 20 homozygous CcS/Dem recombinant congenic strains, each of which contains a different random subset of approximately 12.5% of genes from the susceptible strain STS/A and 87.5% of genes from the relatively resistant strain BALB/cHeA. Some CcS/Dem strains received the alleles from the susceptible strain STS/A at one or more of the multiple colon tumor susceptibility loci and are susceptible, whereas others are resistant. Linkage analysis shows that these susceptibility genes are different from the mouse homologs of the genes known to be somatically mutated in human colon cancer (KRAS2, TP53, DCC, MCC, APC, MSH2, and probably also MLH1). Different subsets of genes control tumor numbers and size. Two colon cancer susceptibility genes, Scc1 and Scc2, map to mouse chromosome 2. The Scc1 locus has been mapped to a narrow region of 2.4 centimorgans (90% confidence interval).

Metalorganic chemical vapor deposition of GaAsN epilayers: microstructures and optical properties

In this article, we investigate the parameters used in the MOCVD growth of GaAsN epilayers on GaAs substrates and some of their microstructures and optical properties. The N incorporation was found to mainly depend on the growth temperature and the fractional 1,1-dimethylhydrazine molar flow. A thin highly strained interface layer was observed between GaAsN and GaAs, which, contrary to previously published results, was not N enriched. The low-temperature (10 K) photoluminescence spectra were composed of several emissions that we attribute to a combination of interband transition and transitions involving localized defect states. (C) 2004 Elsevier B.V. All rights reserved.

Different cation-protonation patterns in mol-ecular salts of unsymmetrical dimethyhydrazine : C2H9N2·Br and C2H9N2·H2PO3

Peer reviewed