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Both epidemiological and experimental findings have indicated that components of Western diets influence colonic tumorigenesis. Among dietary constituents, calcium and cholecalciferol have emerged as promising chemopreventive agents. We have demonstrated that a Western-style diet (WD) with low levels of calcium and cholecalciferol and high levels of (n-6) PUFA, increased the incidence of neoplasia in mouse intestine compared with a standard AIN-76A diet; models included wild-type mice and mice with targeted mutations. In the present study, adenomatous polyposis coli (Apc)(1638N/+) mice carrying a heterozygous Apc mutation were fed either an AIN-76A diet, a WD, or a WD supplemented with calcium and cholecalciferol (WD/Ca/VitD3). Diets were fed for 24 wk and effects on cellular and molecular events were assessed by performing immunohistochemistry in colonic epithelium along the crypt-to-surface continuum. Feeding WD to Apc(1638N/+) mice not only enhanced cyclin D1 expression in colonic epithelium compared with AIN-76A treatment as previously reported but also significantly increased the expression of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) concomitantly with a decrease in the proapoptotic Bcl2-associated X protein and the number of apoptotic epithelial cells. WD treatment enhanced mutant Apc-driven small intestinal carcinogenesis and also resulted in the formation of a small number of colonic adenomas (0.16 +/- 0.09; P < 0.05). By contrast, the WD/Ca/VitD3 diet reversed WD-induced growth, promoting changes in colonic epithelium. Importantly, Apc(1638N/+) mice fed the WD/Ca/VitD3 diet did not develop colonic tumors, further indicating that dietary calcium and cholecalciferol have a key role in the chemoprevention of colorectal neoplasia in this mouse model of human colon cancer. [ABSTRACT FROM AUTHOR]

Flap endonuclease 1 (Fen1) and exonuclease 1 (Exo1) have sequence homology and similar nuclease capabilities. Both function in multiple pathways of DNA metabolism, but appear to have distinct in vivo nucleic acid substrates, and therefore distinct metabolic roles. When combined with Apc1638N, Fen1 promotes tumor progression. Because of functional similarity to Fen1, and because Exo1 is involved in DNA mismatch repair (MMR) by interaction with Msh2 and Mlh1, genes that cause hereditary nonpolyposis colorectal cancer (HNPCC), we investigated the possibility that Exo1 might also act as a modifier to Apc1638N. We present evidence that mice with combined mutations in Apc1638N and Exo1 and Apc1638N, Exo1 and Fen1 genes show moderate increased tumor incidence and multiplicity in comparison to Apc1638N siblings, implying a low penetrance role for Exo1 in early gastrointestinal (GI) tumorigenesis. Despite a decrease in median survival (10 months) in Apc1638N Exo1 mice, their tumors do not progress any more rapidly than those of Apc1638N. Instead these animals die from infections that are the result of impaired immune response. Apc1638N Exo1 Fen1 mice survive longer (18 months), and therefore appear relatively immune competent. They die of invasive GI tumors that display microsatellite instability (MSI). Our results show that Exo1 has a modest tumor suppressor function.Oncogene (2007) 26, 6297–6306; doi:10.1038/sj.onc.1210453; published online 23 April 2007 [ABSTRACT FROM AUTHOR]

The Apc1638N mouse carries a targeted mutant allele at the endogenous adenomatous polyposis coli (Apc) gene and represents a unique in vivo model to study intestinal tumor formation and progression. Heterozygous Apc+/Apc1638N mice progressively develop 5-6 adenomas and adenocarcinomas of the small intestine within the first 6 months of life following a histologic sequence similar to that observed in human intestinal tumors. Here, we present the somatic mutation analysis of a total of 57 tumors. The results indicate that in > or = 75% of the lesions tested the wild type copy of the Apc gene is lost and that this LOH event extends to the entire mouse chromosome 18. Unexpectedly, mutations at the K-, N- and H-ras genes have not been found in these tumors. Immunohistochemical analysis of the Apc1638N tumors failed to detect accumulation of the Tp53 protein. Also, no mutations have been found in exons 7 and 8 of the Tp53 gene. These results indicate that, although the genetic inactivation of Apc is involved in the initiating event of the human as well as murine intestinal tumorigenesis, tumor growth and progression follow different mutational pathways in these two species. [ABSTRACT FROM PUBLISHER]

In order to get more detailed information for better decision makingin future biogenic waste treatment, different processes to treat biogenic wastes in plants with a treating capacity of 10,000 tons of organic household wastes per year were compared. The comparison includedlife cycle assessments as well as economic considerations for different treating methods. Measurements on compost plants showed that methane emissions are higher than estimated so far. With the tools ECOINDICATOR and UBP anaerobic digestion shows to be advantageous as compared to composting, incineration or combination of digestion and composting, mainly because of a better energy balance. In fully enclosed, professional treatment plants, the specific biotechnological treatmentcosts are in the range of about 150.-sFr/ton for aerobic, anaerobic and combined technologies. It can be concluded, that anaerobic processes will become considerably more important in the future mainly for ecological reasons. [ABSTRACT FROM AUTHOR]

Solid organic wastes were codigested together with sludge of a sewage treatment plant (STP). In the practical part of the study, a plant to pretreat the organic solid wastes provided by local super markets was constructed at the STP of Frutigen, Switzerland. Up to more than 1 cubic metre of wastes was added to the fermenter of the STP every day. Data collected during 14 months of practical works, showed that for raw fruit and vegetable wastes a two step pretreatment is necessary: First the wastes were chopped and afterwards reduced to a size of 1-2 millimetres, in order to get a homogeneous suspension together with the primary sludge. The vegetable wastes showed excellent digestibility: They seemed to accelerate the digestion process as well as to increase the degree of the anaerobic degradation of the sludge. The energy demand for both, pretreatment and digestion, was 85 kWh/ton of fresh wastes. 20% of the energy was used for the hygienization, a step which does not seem to be necessary for this kind of waste in most of the cases, however. After using the gas for energy conversion, a net yield of 65 kWh/ton of electricity and 166 kWh/ton of heat was measured. Treating cooked kitchen wastes, the net energy production willbe higher, because in this case a one step pretreatment will be sufficient. The pretreatment and treatment costs for codigestion on STP'swere calculated to be in the range of 55 US$/ton treating half a tonper day and 39 US$/ton treating one ton, respectively. A theoreticalfeasibility study showed that in Switzerland there is a short term potential on STP's for the codigestion of about 120,000 tons of biogenic wastes per year without big investments. Economic studies about codigestion on agricultural biogas plants showed that the codigestion is a must at the current energy prices, which are far too low for agricultural AD without an additional income by treating solid wastes forthird parties. [ABSTRACT FROM AUTHOR]