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Detoxification and Colorectal Cancer Colon cancer is the second most common cause of cancer death in the United States. Though many risk factors have been studied, including genetics and environmental factors, many researchers believe that interactions between diet, the intestinal microflora and the cells in the lining of the colon hold one of the keys to what causes colon cancer to develop. Unfavorable changes in the intestinal microflora, sometimes caused by changes in diet, may increase the risk for developing colon cancer. Regular, daily consumption of probiotics may help maintain a healthy intestinal microflora and promote a healthy environment. Another theory for the cause of colon cancer is that prolonged exposure to cancer-causing compounds in the colon may trigger the process. Although the evidence is not conclusive and much further research is required, probiotics may be beneficial in modulating several major intestinal functions potentially associated with the development of colon cancer. Studies have been conducted on the impact of regular consumption of probiotics and the amount of time certain carcinogens spend in the colon. In addition animal and laboratory studies have also been performed on the effect of probiotics on the formation of cancer causing compounds in colon cells , DNA damage in colon cells and on their binding capacity to carcinogenic compounds, rendering them less harmful. Also, some animal studies have explored probiotics' impact on the premalignant changes in cells caused by a high fat diet. Overall, however, few prospective human studies have been performed on the relation between the consumption of probiotic containing product and colon cancer. A large clinical study is currently underway in the European Union to investigate the effect of probiotics on colon cancer. Probiotics have been shown to have a detoxifying effect in the colon via several mechanisms. Studies have shown that probiotics may impact the production of detoxifying agents in the colon (Saikali et al., 2004). Specifically, probiotics alter colonic phase 1 and phase II detoxifying enzymes (Challa et al., 1997). Lactic acid probiotic bacteria also have an effect on the modulation of the production of enzymes responsible for the release of mutagenic agents within the colon that convert procarcinogenic substances into carcinogens (Goldin et al., 1984). (Lidbeck et al., 1992). Probiotics have an additional detoxifying action by reducing the concentration of bile acids in the colon In vitro studies show that probiotics have the ability to bind with mutagens that are present in the diet (Morotomi et al., 1986). Animal studies have shown that consumption of probiotics reduces the fecal concentration of heterocyclic amines that result from eating meat (Goldin et al., 1984). Probiotics may also have a beneficial effect by altering the composition of the intestinal microflora. A shift in the balance of the intestinal microflora (an increase in the concentration of beneficial bacteria and a reduction in the concentration of putrefactive bacteria, likely involved in the production of undesirable substances) could have a detoxifying effect in the colon (Shahani et al., 1980). (Popiela et al., 2000). Danone Vitapole, Nutrition Research, Palaiseau Cedex, France. Colorectal cancer (CRC) is a major cause of death from cancer in the Western world. Approximately 70% of CRC is associated with environmental factors, probably mainly the diet. There is interest in the potential protective role of fermented milks containing probiotic cultures against CRC. This article analyzes the existing data from human, animal, and in vitro studies that explore whether consumption of milks fermented with probiotic cultures could play a role in colon cancer risk reduction. Cohort studies have failed to detect significant effects, but most case-control studies favor a protective role of fermented milks against colon cancer. Interventional studies have shown a shift of intermediate markers of CRC risk in human subjects from a high- to low-risk pattern after ingestion of fermented milks or probiotics. Animal studies consistently show a reduction in chemically induced colorectal tumor incidence and aberrant crypt formation accompanying probiotic administration. In vitro studies also provide evidence of protection, and permit a better understanding of active compounds involved, and of the mechanisms underlying their anticarcinogenic effects. Probiotics may beneficially modulate several major intestinal functions: detoxification, colonic fermentation, transit, and immune status, which may accompany the development of colon cancer. Although the evidence is not conclusive and much further research is required, the data reviewed constitute a promising body of evidence supporting the protective role of milks fermented with probiotic cultures in colon cancer risk reduction. Return Challa A, Rao DR, Chawan CB, Shackelford L. Department of Food Science and Animal Industries, Alabama A&M University, Normal 35762, USA. Bifidobacterium longum has been shown to afford protection against colon tumorigenesis. Lactulose, a keto analog of lactose, serves as a substrate for preferential growth of Bifidobacterium. It is not known whether feeding lactulose along with B. longum will have any advantage over feeding of B. longum alone. To test this combination effect, 61 male Fisher 344 weanling rats were divided into four groups of 15 rats each (16 in the control group) and assigned to one of the following four diets for 13 weeks: (i) AIN76A (control, C); (ii) C + 0.5% B. longum (C+Bl, containing 1 x 10(8) viable cells/g feed); (iii) C + 2.5% lactulose (C+L); (iv) C + 0.5% B. longum + 2.5% lactulose (C+Bl+L). All animals received a s.c. injection of azoxymethane at 16 mg/kg body wt at 7 and 8 weeks of age. Colons of 10 rats from each dietary group were analyzed for aberrant crypt foci (ACF), which are preneoplastic markers. Colonic mucosa and livers from five rats were analyzed for glutathione S-transferase (GST, a Phase II enzyme marker). Results indicate that feeding of lactulose and B. longum singly and in combination reduces the number of ACF (P = 0.0001) and the total number of aberrant crypts significantly (P = 0.0005). The total number of ACF in diets C, C+Bl, C+L and C+Bl+L were 187 +/- 9, 143 +/- 9, 145 +/- 11 and 97 +/- 11 respectively. There was no significant difference in weight gain among treatments. Colonic mucosal GST levels were significantly (P = 0.05) higher in the Bl and L groups compared with group C. Initially there was a mild diarrhea in lactulose-fed rats. There was a positive correlation between higher cecal pH and number of ACF. Results of the study indicate that Bifidobacterium and lactulose exert an additive antitumorigenic effect in rat colon. Return Goldin BR, Gorbach SL. F344 rats were fed compounds containing a nitro, azo, or amine-glucuronide group-2-nitronaphthalene (CAS: 581-89-5), 2-nitrofluorene (CAS: 607-57-8; 2-nitro-9H-fluorene), 4-phenylazo-2-naphthol (CAS: 6410-10-2; 1-[(4-nitrophenyl)azo]-2-naphthol), and 2-naphthylamine-N-D-glucuronide--and the formation of free amines was measured in the feces. The effects of diet (mean vs. grain), administration of antibiotic, and the feeding of Lactobacillus acidophilus were evaluated. Meat-fed rats given 2-nitronaphthalene had approximately 4 times higher concentration of free amines in their feces as compared to the concentration in grain-fed rats. In a similar experiment with 2-naphthylamine-N-D-glucuronide, the meat-fed animals had approximately 1.5 times more of the free amines and 50% less of the conjugates in their feces. When meat-fed animals were given L. acidophilus with 2-nitrofluorene or 2-naphthylamine-N-D-glucuronide, they had significantly lower free amines and higher concentrations of conjugates in their feces than did the meat-fed controls. Similarly, erythromycin or tetracycline decreased the fecal amine production in meat-fed animals that had received 2-nitrofluorene or 4-phenylazo-2-naphthol. In another experiment, erythromycin inhibited the production of free amines from 2-naphthylamine-N-D-glucuronide in rats fed a high-fat diet. Studies of fecal enzymes revealed lower levels of beta-D-glucuronidase, nitroreductase, and azoreductase in grain-fed rats and in meat-fed animals also given antibiotics or lactobacilli. These experiments showed that intestinal flora have the ability to convert exogenously administered aromatic nitro and azo compounds and an amine-glucuronide compound to free amines. The rate of these conversions was affected by diet and by oral administration of antibiotics and lactobacilli. Return Lidbeck A, Nord CE, Gustafsson JA, Rafter J. Department of Microbiology, Huddinge University Hospital, Karolinska Institute, Sweden. Lactobacilli belong to the normal oropharyngeal and intestinal microflora in humans. These microorganisms contribute to the stabilization of the microflora and maintain the colonization resistance against pathogens. Lactobacilli have been used as dietary supplements in order to prevent gastrointestinal disturbances. Claims have been made that certain strains of lactobacilli possibly exert anticarcinogenic activities. The activity of bacterial enzymes, implicated in colon carcinogenesis may be elevated by a high meat, Western-type diet. Supplements of Lactobacillus acidophilus decreased these levels in both rats and humans. Colon cancer patients given L. acidophilus fermented milk showed a significant increase both in numbers of intestinal lactobacilli and dietary calcium intake, while decreasing trends in levels of both soluble faecal bile acids and faecal bacterial enzymes, two risk makers for colon cancer, were observed. In vitro studies have revealed that lactobacilli and other lactic acid bacteria have the ability to absorb cooked food mutagens. Recent studies in humans have shown that intake of L. acidophilus significantly reduced the mutagen excretion after consumption of fried meat. Several mechanisms by which lactobacilli might exert anticarcinogenic effects are discussed. Thus, certain strains of lactobacilli might lower the colon cancer risk in humans. Return Morotomi M, Mutai M. The ability of 22 strains of intestinal bacteria to bind the mutagenic pyrolyzates--3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole [(Trp-P-1) CAS: 62450-06-0], 3-amino-1-methyl-5H-pyrido [4,3-b]indole [(Trp-P-2) CAS: 62450-07-1], 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-1) CAS: 67730-11-4], 2-aminodipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-2) CAS: 67730-10-3], 2-amino-3-methylimidazo[4,5-f]quinoline [(IQ) CAS: 76180-96-6], 2-amino-3,4-dimethylimidazo[4,5-f]quinoline [(MeIQ) CAS: 77094-11-2], and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [(MeIQx) CAS: 77500-04-0]--was investigated and compared to their ability to bind to some dietary fibers (corn bran, apple pulp, soy bean fiber, cellulose, chitin, and chitosan). The pyrolyzates are potent mutagenic and carcinogenic heterocyclic amines formed during cooking. Solution of these amines was mixed with aqueous suspension of bacterial cells or dietary fibers, and removal of these amines from the reaction mixture by centrifugation was defined as the binding. Trp-P-1 and Trp-P-2 were effectively bound to all gram-positive and some gram-negative bacterial cells, corn bran, apple pulp, and soy bean fiber. Binding of Trp-P-1 and Trp-P-2 to Escherichia coli, Klebsiella pneumoniae, and cellulose was moderate, and to chitin and chitosan it was little. None but corn bran bound Glu-P-1 and Glu-P-2 effectively. Corn bran effectively bound all mutagens tested. The quantity of the binding of IQ, MeIQ, and MeIQx was dependent on the strain of bacteria and the kind of fiber. The mechanism of binding of Trp-P-2 to freeze-dried feces, Lactobacillus casei YIT 9018 (LC9018), and corn bran was investigated. The binding was pH dependent, occurred instantaneously, and was inhibited by the addition of metal salts. These results indicate that the binding was mostly due to a cation-exchange mechanism, but some irreversible binding of Trp-P-2 was observed, most notably to freeze-dried feces. The mutagenicity of Trp-P-2 for Salmonella typhimurium TA98 in the presence of S9 mix was inhibited by the addition of LC9018 or corn bran to the reaction mixture. The results indicate that bound Trp-P-2 did not cause mutation under the assay conditions. Return Popiela T, Kulig J, Klek S, Wachol D, Bock PR, Hanisch J. 1st Department of General and Gastrointestinal Surgery, Jagiellonian University, Krakow, Poland. All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life. Return 
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