Min mice

PERRIN F, PERRIN P, CHAMP M, BORNE, F, MEFLAH K, MENANTEAU J (1997) Short-chain frUCtO-oligosaccharides rednce the occurrence of colon tumor and develop gut-associated lymphoid tissue in Min mice. Cancer Res. 57 225-8. 

Kang, S.Y. et al., Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce prohferation of human colon cancer cells. Cancer Lett., 194, 13, 2003. 

LC0i values for four time periods were provided by E.I. du Pont de Nemours (1981) for the rat. They are as follows 5 min, 283 ppm 15 min, 138 ppm 30 min, 127 ppm and 60 min, 88 ppm. Ballantyne (1983) used several concentrations and exposure durations but did not provide the actual concentrations therefore, an LCqi could not be calculated. Matijak-Schaper and Alarie (1982) reported no deaths in mice inhaling HCN at 100 ppm for 30 min. Mice inhaling HCN at 30 ppm for 24 h showed signs of lung congestion (Pryor et al. 1975). 

LC50 (inhalation) for guinea pigs 25 pph/30-min, mice 10 pph/30-min, rabbits 25 pph/30-min (quoted, RTECS, 1985). 

IC50 (nM) (Leukaemia cells CCRF-CEM) 3.2 Plasma half life (min) (mice) 212 88... 

Suganuma M, Ohkura Y, Okabe S, Fujiki H. 2001. Combination cancer chemoprevention with green tea extract and sulindac shown in intestinal tumor formation in Min mice. J Cancer Res Clin Oncol 127 69-72. 

Ziegler CC, Rainwater L, Whelan J, McEntee MF. 2004. Dietary resveratrol does not affect intestinal tumorigenesis in Apc(Min/ + ) mice. J Nutr 134 5-10. 

In vivo studies using mouse models have proved that curcumin modifies apoptosis resistance, leading to the inhibition of tumor formation and the prevention of adenoma development in the intestinal tract. The chemopreven-tive effect of curcumin for intestinal tumors in Min/+ mice was investigated. A dietary level of 0.15% curcumin decreased tumor formation in Min—/— mice by 63%. Examination of intestinal tissue from the treated animals showed the tumor prevention by curcumin was associated with increased enterocyte apoptosis and proliferation. Curcumin also decreased expression of the oncoprotein (S-catenin in the erythrocytes of the Min/+ mouse, an observation previously associated with an antitumor effect. Curcumin enhanced PhlP-induced apoptosis and inhibited PhIP-induced tumorigenesis in the proximal small intestine of Ape (min) mice. Experiments performed on intestinal tumors in C57BL/6J-Min/+ (Min/+) mice demonstrated that curcumin has a regulatory role in lymphocyte-mediated immune function [Churchill et al., 2000]. Furthermore, levels of COX-2 protein expression have been found to reflect the retardation of adenoma development in mouse intestines after treatment with curcumin [Tunstall et al., 2006]. 

Oikarinen, S, Pajari, A., Salminen, I., Heinonen, S.M., Adlercreutz, H., and Mutanen, M. 2005. Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice. Br. J. Nutr. 94, 510-518. 

The roles of sphingolipids in chemoprevention have also been reported previously (Borek and Merrill, 1993). Administration of SM in the diet prevents the formation of chemically induced colon cancer tumors and aberrant colonic crypts by decreasing the rate of cell proliferation and increasing apoptosis in mice (Schmelz et ah, 1996). Diets supplemented with ceramide, SM, glucosyl-ceramide, lactosylceramide, or ganglioside GD3 to C57B1/6 J(Min/ + ) mice with a truncated APC gene product, reduced the number of tumors in the intestine (Schmelz et al., 1996, 2000). 

The Cu-Zn-SOD-mimetic activity of Cu(II)(3,5-DIPS)2 and its lipid solubility were criteria used to select this complex in the initial attempt to study a copper complex as a radioprotectant. This complex was found to prevent death in 58% of the lethally irradiated (10 Gy, 0.4Gy/min) mice when they were thought to have been treated with 0.49 mmol/kg, 3 h before irradiation [505]. Subsequent studies revealed that this protection could be achieved with a much lower dose of complex suspended in a propyleneglycol-poly(vinyl alcohol)-saline vehicle. Treatment with 0.16 mmol/kg produced a 60% increase in survival in similarly irradiated and treated mice [506]. Most recent studies suggest that this radioprotectant effect may be achieved with a still further reduced dose of 0.04 mmol/kg and this lower dose appears to be as effective if given 3 h after irradiation as it is when given 3 h before irradiation. 

Lai et al. " note that the DNA mismatch-repair-deficient Min mouse model (Apc+/-Msh2-/-) has genetic features of both FAP and HNPCC and, most importantly, rapidly develops numerous small and large bowel adenomas as well as colonic aberrant ciypt foci. They investigated the effects of COX inhibitors on intestinal adenomas and colonic aberrant crypt foci in this accelerated-polyposis, mismatch-repair-deficient Min mouse model, in addition to a standard Min mouse model. Their smdy demonstrated that a specific COX-2 inhibitor is effective in preventing small-bowel polyps in mismatch-lepair-deficient Min mice and both small- and large-bowel polyps in standard Min mice. 

Tangeretin from citrus Small intestinal tumors in min/- - mice... 

Min mice have a truncating mutation in the murine APC gene at a position similar to that found in many FAP patients and develop multiple intestinal adenomas [24]. Heterozygous APC mice were therefore used to evaluate the efficacy of potential chemopreventative compounds on development of intestinal polyps [25]. The compounds tested were sulindac, a non-steroidal anti-inflammatory drag with estabUshed chemopreventative activity, and EKB-569, an irreversible inhibitor of the epidermal growth factor receptor kinase. 

It is important to note that the modifications generated by those lipid oxidation products contribute nearly to the same extent to DNA damage than the direct oxidized bases (Winczura et al. 2012). These lipid peroxidation aldehydes-DNA adducts have been reported in vivo in rodent and human DNA, in a wide variety of organs and tissue. For most of them, they can be found at a basal state (Marnett 1999 Nair et al. 1999, 2007), but their concentration is increased in the case of oxidative stress due, for instance, to inflammatory processes (Nair et al. 2007), but also in the case of PUFA-rich diet (Fang et al. 2007). For etheno-adducts, most of the studies report the presence of unsubstituted adducts, making the identification of the reactant enal impossible. However, a substituted etheno-adduct specific to the lipid oxidation product 4-oxo-nonenal has been found in greater amounts in the small intestine of mice prone to intestinal cancer (Min mice) and overexpressing the enzyme COX-2 involved in inflammatory processes than in the small intestine of control mice (Williams et al. 2006). 

Williams MV, Lee SH, Pollack M, Blair lA. Endogenous lipid hydroperoxide-mediated DNA-adduct formation in Min mice. J Biol Chem 2006 281 10127-10133. 

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