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PubMed2001

Effect of lactobacilli, bifidobacteria and inulin on the formation of aberrant crypt foci in rats.

BACKGROUND: Our studies were aimed at investigating the effect of lactic acid producing bacteria (LAB) or inulin, a natural source of non-digestible oligosaccharides derived from chicory, on the induction by carcinogens of aberrant crypt foci (ACF) in the colon, which are considered to be early precursor lesions of neoplasia. METHODS: Strains of Bifidobacterium longum, Lactobacillus casei and Lactobacillus acidophilus were administered to rats fed a purified high starch diet, under a variety of treatment protocols including daily gavage, via the drinking water and in the diet. The rats were treated with methyl-N-nitrosourea, 1,2-dimethylhydrazine, or azoxymethane (AOM) to induce ACF. RESULTS: In general, no consistent significant changes in ACF numbers were detected in these experiments. In one study, the basal diet of the rats was changed to one containing a higher level of fat (corn oil). Under these conditions, a significant decrease in AOM-induced colonic ACF was seen in rats given L. acidophilus or inulin. In a concurrent group of animals fed a low fat diet, no significant decrease in ACF was observed. CONCLUSIONS: The results indicate that the type of diet fed can influence the detection of protective effects of LAB and oligosaccharides and that against the background of a diet with a level of fat typical of a Western diet, evidence for a protective effect of L. acidophilus and inulin towards colon cancer was obtained

1,2-Dimethylhydrazine↗
PubMed1982

Metabolism of 1,2-dimethylhydrazine in isolated perfused rat liver.

The metabolism of 1,2-dimethylhydrazine (DMH) was investigated in isolated perfused rat liver. The separation of [14C]DMH and its metabolites azomethane (AM), azoxymethane (AOM) and methylazoxymethanol (MAM) was performed by high pressure liquid chromatography (HPLC). The fractions were quantitatively detected by liquid scintillation counting of the radioactivity. It was demonstrated that DMH is highly metabolized by the liver. After 1 h of perfusion, the median amounts of DMH and its metabolites in the medium were: DMH, 16%; AM, 3%; AOM, 42%; MAM, 30% of the given dose. During this time 9.9% and 0.7% of the total radioactivity were eliminated as AM and CO2 in the oxygen stream of the perfusion apparatus; 0.6% were excreted by bile and 12.3% stored in hepatic tissue. The reaction rate (t1/2) of each individual metabolic step was estimated by means of a mathematical kinetic model as follows: DMH leads to AM, 21.8 min; AM leads to AOM, 1.5 min; AOM leads to MAM, 41.5 min; MAM leads to, 611 min. The results are discussed in comparison to in vivo experiments.

1,2-Dimethylhydrazine↗
PubMed1995

Dietary omega-3 fats reduce proliferation and tumor yields at colorectal anastomosis in rats.

BACKGROUND & AIMS: Colorectal anastomoses show increased mucosal crypt cell proliferation rates (CCPRs) and often form the site for tumor recurrence after resection of colorectal cancer. The aim of this study was to assess the effects of a 20% omega-3 fat diet on CCPRs and anastomotic tumor formation compared with an isocaloric 20% saturated fat diet in experimental colorectal cancer. METHODS: One hundred sixty male Wistar rats were administered azoxymethane or saline for 6 weeks, after which a colonic anastomosis or sham operation was performed. CCPR, mucosal fatty acids, and tumor yield were analyzed at the anastomosis and proximal and distal colon sites at 15 and 23 weeks. RESULTS: Diet, carcinogen treatment, and surgery all had significant effects on CCPR with omega-3 fats producing the lowest CCPR at all sites. There were fewer tumors (P < 0.02), including a marked reduction of anastomotic tumors in omega-3 fat-fed animals that was associated with a significant reduction of arachidonic acid in mucosal and tumor lipids. CONCLUSIONS: Dietary omega-3 fat significantly reduced colonic CCPR and tumor yield, including at the site of anastomosis. Dietary omega-3 fats may be of value to patients after colorectal resection and anastomosis for cancer and warrant further testing.

Anastomosis, Surgical↗
PubMed1990

The effects of carrageenan on drug-metabolizing enzyme system activities in the guinea-pig.

Carrageenans are seaweed extracts comprising high molecular weight sulphated polygalactosides. They are used in foods at concentrations of up to 2.5% as thickening and gelling agents. When degraded to lower molecular weight forms, they have been shown to induce ulcerative colitis and colon cancer in laboratory animals. Furthermore, undegraded carrageenan (CG) has been shown to promote azoxymethane and methylnitrosourea initiated carcinogenesis, but the promotion mechanism is unclear. To determine if this mechanism involves alterations of tissue drug-metabolizing enzyme system (DMES) activities, six groups of five guinea-pigs each were administered 0.2% kappa undegraded, 0.2% i undegraded, 1% kappa degraded or 1% i degraded CG, or control solutions in the drinking-water for 8 wk. Microsomal and cytosolic DMES activities of the liver, small intestine and colon were determined. The kappa undegraded CG group exhibited significant (P less than 0.05) increases in small intestine cytochrome P-450 levels and benzo[a]pyrene hydroxylase activities. These data suggest that undegraded CG may selectively induce DMES activities in the small intestine mucosa.

Aminopyrine N-Demethylase↗
PubMed1992

Flaxseed supplementation and early markers of colon carcinogenesis.

Since flaxseed ingestion produces potentially anticarcinogenic lignans in the colon, this study determined whether flaxseed decreases the risk for colon carcinogenesis. Following a single injection of azoxymethane (15 mg/kg body wt.), five groups of male Sprague-Dawley rats were fed a high-fat (20% corn oil) basal diet with or without supplementation with 5% or 10% flaxseed meal (FM) or flaxseed flour (FF) for four weeks. Upon sacrifice, colons were examined for aberrant morphology and cell proliferation. In the descending colon of supplemented groups, the total number of aberrant crypts and foci were significantly reduced by 41-53% and 48-57%, respectively. The labeling index (LI) was also 10-22% lower in these groups, except for the 5% FM group. While these effects are not linearly related to the level of flaxseed fed, it suggests that flaxseed feeding may reduce the risk for colon carcinogenesis.

Animals↗
PubMed1993

Potential synergism between wheat bran and psyllium: enhanced inhibition of colon cancer.

In this study we compared the influence of high fat (20% w/w) diets that combine low levels of calcium (0.18% w/w) and low (1% w/w), medium (4% w/w) and high (8% w/w) levels of dietary fiber from wheat bran (WB), with high (8% w/w) levels of dietary fiber from psyllium (PS) alone or in various combinations with WB, on the induction of colon tumors in Fischer-344 rats following exposure to azoxymethane (AOM). The rats were fed the experimental diets for 2 weeks, and then were given two s.c. injections of AOM (15 mg/kg body wt./week). Twenty-three weeks following the first injection of AOM, the incidence of colon tumors in the different dietary groups (12 rats/group) was compared. The results clearly showed that by increasing the dietary fiber concentration of WB from 1 to 8% significantly reduced the number of colon tumors/group. When the influence of 8% dietary fiber from WB on the development of colon tumors was compared with that of PS (WB:PS = 0:100), no significant difference was observed. However, combinations of WB and PS showed a greater protective effect than either WB or PS alone, at comparable levels of dietary fiber. The 50:50 combination of WB and PS showed maximum protection, while 25:75 and 75:25 combinations both produced intermediate effects. None of the diets showed any significant effect on the normal growth of rats. The results indicate that WB and PS fiber alone, and to a greater degree in combination, can offer protection against colon cancer promoted by high fat, low calcium diets. Diets that include wheat bran in combination with psyllium could be an effective means of reducing colon cancer risk in human populations addicted to high risk western diets.

Animals↗
PubMed1994

The effect of chenodeoxycholic acid on the development of aberrant crypt foci in the rat colon.

Bile acids are reported to enhance experimentally-induced colonic tumorigenesis. Previously we have reported that cholic acid, a known tumor promoter, actually reduced the number of aberrant crypt foci (ACF), purported preneoplastic lesions (B.A. Magnuson and R.P. Bird, Cancer Lett., 68 (1993), 15-23). This observation was unexpected and has prompted us to explore the effect of other bile acids on the development of ACF. The primary objective of this investigation was to evaluate the effect of feeding varying dosages of chenodeoxycholic acid (CDC) on the induction and growth of ACF and on the proliferative indices of the colonic epithelium. Sprague-Dawley male rats were injected with azoxymethane (+AOM, 20 mg/kg) or saline (-AOM). One week later they were randomly allocated to five groups and were fed diets containing CDC at varying levels (0.0, 0.025, 0.05, 0.1 and 0.2% by weight) for 2 weeks. After completion of the feeding period the number and crypt multiplicity of ACF were quantified, and three different proliferative indices, including mitotic index, BUDR labelling index (percentage S-phase cells) and proliferating cell nuclear antigen labelling index (percentage cycling cells) were determined. CDC at all dosages increased the number of ACF having the maximum effect at the 0.1% CDC level. A significant dose-related increase in crypt height was noted in CDC-fed+AOM groups when compared with the +AOM control groups. The mitotic indices of colonic crypts were higher (P < or = 0.05) only in the 0.025% CDC -AOM group when compared with the 0% CDC -AOM group (5.97 +/- 0.63 vs. 3.92 +/- 0.79). The BUDR labelling indices were not altered by CDC feeding (P > or = 0.05). PCNA labelling indices increased consistently among the CDC-fed groups. Among the -AOM group the 0.05% CDC group had the maximum value, which was significantly different from the control value (19.21 +/- 1.92 vs. 10.93 +/- 0.56, respectively). Among the +AOM groups the PCNA labelling indices increased with increasing levels of CDC. It was concluded that CDC stimulated the development of ACF and altered cell cycle associated events in colonic crypts undergoing neoplastic changes.

Animals↗
PubMed1995

Inhibition of progression of aberrant crypt foci and colon tumor development by vitamin E and beta-carotene in rats on a high-risk diet.

In this study we evaluated the effect of dietary administration of a high-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carotene or folic acid and wheat bran on the growth of pre-existing aberrant crypt foci (ACF) that had been induced in Fischer-344 rats exposed to azoxymethane (AOM) and a HRD for 10 weeks. The rats (25 rats/dietary group) were fed a HRD for 2 weeks and were then given 2 subcutaneous injections of AOM (15 mg/kg body weight) while the rats continued on the HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitamin E, beta-carotene, folic acid or wheat bran. At 10, 14 and 18 weeks after the initiation of the experiment, 5 rats from each group were killed and the number of aberrant crypt foci (ACF) with different multiplicities were compared between groups. The dietary intervention was continued for 30 weeks to determine whether the inhibitory effect on the growth of ACF influenced the subsequent development of colonic tumors. The results revealed that vitamin E and beta-carotene caused a significant decrease in the number of ACF of different multiplicities when compared to the effect of the HRD alone. The decrease in the number of ACF due to folic acid and wheat bran appeared to be much smaller and in most cases was not significant. However, there was also a significant decrease in the incidence of colonic tumors and tumor multiplicity in both the vitamin E and beta-carotene groups that was not seen in the control group. The reports clearly demonstrates the ability of vitamin E and beta-carotene to inhibit the growth of colonic ACF, even in the presence of the strong promoting effect of high levels of dietary fat, using a post-initiation experimental design.

Animals↗
PubMed1996

A possible medium-term assay for detecting the effects of liver and colon carcinogens in rats.

The aim of the present study was to verify whether the tumorigenic effect of a rat liver carcinogen, 2-acetylaminofluorene (AAF), and of a promoter of rat colon carcinogenesis, chenodeoxycholic acid (CDCA), could be detected with a single medium-term assay using as markers gamma-glutamyltranspeptidase (GGT)-positive foci in the liver and aberrant crypt foci (ACF) in colon mucosa. In rats given in the first 2 weeks of treatment both N-nitrosodiethylamine (NDEA), as initiator of liver carcinogenesis, and azoxymethane (AOM), as initiator of colon carcinogenesis, the subsequent 6-week feeding on a diet containing AAF (0.01%) produced a significant marked increase of the number and area of GGT-positive foci which is consistent with the results of long term assays. When rats initiated with both NDEA and AOM were fed for 6 weeks on a diet containing CDCA (0.1%) a significant increase of large ACF as well as of crypt multiplicity was observed, consistently with the promoting effect of CDCA in colon carcinogenesis. The results obtained in this preliminary study suggest that this medium-term assay might be able to screen both liver and colon carcinogens in rats.

Animals↗
PubMed1996

Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ).

The aberrant crypt foci (ACF) bioassay has been used extensively to study the early effects of different dietary components on the colonic mucosa of laboratory rodents. ACF are proposed to represent preneoplastic lesions of colon cancer. Compared to the normally used initiators 1,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis. In the present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can be modulated by the amount of refined carbohydrates in the diet. Rats given a high sucrose/dextrin diet showed a significantly higher number of ACF compared to rats given a diet high in starches. The effect on tumor outcome will await the termination of a ongoing parallel study.

Administration, Oral↗
PubMed2004

Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours.

The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2% curcumin (CUR), 4% rutin (RUT) or 0.04% benzyl isothiocyanate (BIT) for 8 months. ACF were counted after 7, 15 and 26 weeks. Tumours were scored after 26 weeks and 8 months. We found that the WB and CUR diets inhibited the development of colorectal tumours. In contrast, the RUT and BIT diets rather enhanced (although not statistically significantly) colorectal carcinogenesis. In addition, the various compounds caused different effects on the development of ACF. In most cases the number or size of ACF was not predictive for the ultimate tumour yield. The expression of some tumour-related genes was significantly different in tumours from the control group as compared to tumours from the treated groups. It was concluded that WB and CUR, as opposed to RUT and BIT, protects against colorectal cancer and that ACF are unsuitable as biomarker for colorectal cancer. Effects of the different dietary compounds on metalloproteinase 1 (TIMP-1) expression correlated well with the effects of the dietary compounds on the ultimate tumour yield.

Animals↗
PubMed2005

Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early event during premalignant colonic epithelial hyperproliferation.

Hyperproliferation of the premalignant epithelium is critical for colonic carcinogenesis; however the mechanisms remain largely unexplored. We report herein that prior to occurrence of neoplastic lesions in the azoxymethane-rat model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase (Csk) was down-regulated with a concomitant increase in Src activity. Furthermore, pharmacological or genetic (RNA interference) inhibition of Csk resulted in increased proliferation in colon cancer cell lines through the mitogen-activated protein kinase dependent pathway. Thus, we demonstrate, for the first time, that Csk suppression is an important early event in colorectal cancer pathogenesis.

Animals↗
PubMed2005

Matrix metalloproteinase-9 contributes to brain extravasation and edema in fulminant hepatic failure mice.

BACKGROUND/AIMS: Fulminant hepatic failure (FHF) can be dreadful. When coma sets in, brain edema develops taking FHF into a lethal course. Mechanisms of brain extravasation leading to brain edema remain incompletely understood. Matrix metalloproteinase (MMP)-9 is implicated in various brain injuries. We hypothesized that MMP-9 contributes to brain edema in FHF. METHODS: MMP-9 and its proform were assayed using SDS-PAGE and in situ gelatin zymographies. Brain extravasation was assessed with Evans blue. Brain water was determined by specific gravity and astrocytic endfoot swelling by electron microscopy. FHF in mice was induced by azoxymethane. MMP inhibitor GM6001 and MMP-9 monoclonal antibody were used. RESULTS: Active MMP-9 was significantly increased at the onset of coma and brain extravasation in FHF mice. Blocking MMP-9 with either GM6001 or MMP-9 monoclonal antibody significantly attenuated brain extravasation, astrocytic endfoot swelling, and brain edema. Brains of FHF mice did not show MMP-9 activity. In contrast, livers of these animals showed marked up-regulation of MMP-9 activity. CONCLUSIONS: Our findings suggest that MMP-9 contributes to the pathogenesis of brain extravasation and edema in FHF. The necrotic liver is the source of MMP-9 in FHF. Inhibition of MMP-9 may protect against the development of brain edema in FHF.

Animals↗
PubMed2005

Chemoprevention of chemically-induced mammary and colon carcinogenesis by 1alpha-hydroxyvitamin D5.

Epidemiological data as well as experimental models yield evidence for a protective effect of vitamin D against the genesis of several types of cancers. Given its toxic properties at effective concentrations, numerous analogs of vitamin D have been developed. We synthesized an analog of vitamin D(5), 1alpha-hydroxy-24-ethylcholechalciferol (1alpha(OH)D(5)) and previously reported on its anti-proliferative activities against several cancer cell lines. To further examine its chemopreventive potential, experiments were conducted to investigate the in vivo effects of 1alpha(OH)D(5) using the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model. Results showed that 1alpha(OH)D(5) (25 and 50microg/kg diet) decreased the incidence and multiplicity of mammary tumors in female Sprague-Dawley rats. In a subsequent study, the stage specific inhibition was investigated using the 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis model. While supplementation with of 1alpha(OH)D(5) (40microg/kg diet) showed no significant effects during the initiation phase, tumor incidence during the promotional stage was significantly (p<0.05) decreased by 37.5%. In the colon, 1alpha(OH)D(5) (25microg/kg diet) was highly effective (p<0.001) in inhibiting the development of azoxymethane (AOM)-induced Aberrant crypt foci (ACF) in CF-1 mice. Studies on the stage specific inhibitory effects of 1alpha(OH)D(5) in the colon demonstrated that animals receiving 1alpha(OH)D(5) (25microg/kg diet) during the initiation, promotion, and entire period had a reduction in ACF number of 71, 80 and 82%, respectively. Immunohistochemistry studies comparing the colons of animals receiving control versus 1alpha(OH)D(5) supplemented diets showed that 1alpha(OH)D(5) partly mediates its effects by regulating members of the oncogenic beta-catenin pathway. 1Alpha(OH)D(5) inhibited expression of beta-catenin and peroxisome proliferator-activated receptor beta, a beta-catenin-TCF-4 responsive gene, whereas it induced expression of VDR. Cumulatively, these studies support the chemopreventive properties of 1alpha(OH)D(5) against the development of breast and colon cancers.

Animals↗
PubMed2004

Insulin-like growth factor-binding protein 3 inhibits growth of experimental colocarcinoma.

BACKGROUND: We have previously shown that an important cell growth regulatory protein, insulin-like growth factor-binding protein 3 (IGFBP-3) is depleted in peripheral blood after open--but not laparoscopic--surgery. We have also demonstrated that IGFBP-3 induces apoptosis of human colon cancer cells in vitro. We report here the effect of IGFBP-3 on the growth of colonic epithelial cells in vivo. METHODS: Two tumor models were used: chemically induced carcinogenesis with azoxymethane (AOM) and inoculation of syngeneic colon cancer cells. In AOM-induced carcinogenesis, wild type (WT) and IGFBP-3 transgenic (IGFBP-3-TG) CD1 mice were injected with AOM and the number of aberrant crypt foci (ACF) in the colon studied. In the syngeneic model, BALB/c mice were inoculated with CT26 cells. The control group received saline, while the test group was administered IGFBP-3 weekly. Tumor weight was assessed 2.5 weeks after establishment. RESULTS: The number of aberrant crypt foci was significantly lower in IGFBP-3 transgenic mice (1.3 +/- 1.1) compared to WT controls (6.8 +/- 6.0) (P < .001). Further, CT26 tumors were significantly smaller in BALB/c mice that received IGFBP-3 (0.364 +/- 0.165 g) than in WT controls (0.742 +/- 0.261 g) (P < .01). CONCLUSIONS: IGFBP-3 inhibits the development of colonic tumors in experimental models and may hold promise as an adjuvant therapy for patients with neoplasms.

Adenocarcinoma↗
PubMedDate not supplied

Promotion versus suppression of rat colon carcinogenesis by chlorophyllin and chlorophyll: modulation of apoptosis, cell proliferation, and beta-catenin/Tcf signaling.

The carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the rat that contain mutations in beta-catenin, but the mutation pattern can be influenced by exposure to dietary phytochemicals, such as the water-soluble derivative of chlorophyll called chlorophyllin. Whereas chlorophyllin is an effective blocking agent during the initiation phase, post-initiation responses depend upon the exposure protocol, and can be influenced by the initiating agent and the concentration of chlorophyllin. Post-initiation treatment with 0.001% chlorophyllin (w/v) in the drinking water promoted colon carcinogenesis in the rat, but much higher concentrations (1.0% chlorophyllin) led to suppression. Bromodeoxyuridine and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) indices revealed that the promotional concentration of 0.001% chlorophyllin increased the ratio of cell proliferation to apoptosis in the colonic crypts, whereas concentrations in the range 0.0l-1.0% chlorophyllin modestly reduced this ratio. Molecular studies showed that the spectrum of beta-catenin mutations was markedly different in chlorophyllin-promoted colon tumors--many of the mutations led to direct substitutions of critical Ser/Thr residues within the glycogen synthase kinase-3beta (GSK-3beta) region, whereas in all other groups, including DMH and IQ controls, the mutations typically affected amino acids adjacent to Ser(33). Substitution of critical Ser/Thr residues caused beta-catenin and c-Jun proteins to be markedly over-expressed compared with tumors in which the mutations substituted amino acid residues flanking these critical Ser/Thr sites. In a separate study, rats were exposed to IQ or azoxymethane (AOM), a metabolite of DMH, and they were treated post-initiation with chlorophyllin, chlorophyll, copper, or phytol in the diet. Natural chlorophyll (0.08%) suppressed AOM- and IQ-induced aberrant crypt foci (ACF), whereas chlorophyllin had no effect and copper promoted the number of small ACF induced by IQ. The results suggest that further investigation of the dose-response for suppression versus promotion by chlorophyll and chlorophyllin is warranted, including studies of the beta-catenin/Tcf signaling pathway and its influence on cell proliferation and apoptosis in the colonic crypt.

1,2-Dimethylhydrazine↗
PubMed2002

In vitro and in vivo treatment of colon cancer by VIP antagonists.

Vasoactive intestinal peptide (VIP) is secreted from many cancer lines and VIP binding was observed in many tumors. We have shown before that VIP antagonists are potent inhibitors of neoplastic growth of neuroblastoma, lung and breast cancer cells in vitro. Here, the cultured colon cancer cell line HCT-15 that exhibited VIP receptor expression was treated with the VIP hybrid antagonist neurotensin(6-11)VIP(7-28). The antineoplastic activity was assessed by thymidine incorporation. Neurotensin(6-11)VIP(7-28) efficiently inhibited cancer growth with a maximal effect at nanomolar concentrations. Once the inhibitory properties of the VIP antagonist on colon cancer cells were established, the in vivo curative effects were analyzed. Sprague-Dawley rats were injected with azoxymethane (AOM) (15 mg/kg/week) for 2 weeks, providing artificial induction of colon tumors. The rats were then allocated into four experimental groups: (1) receiving no treatment; (2) receiving treatment with saline; (3, 4) receiving treatment with 10 or 20 microg of neurotensin(6-11)VIP(7-28), respectively. After 10 weeks of daily injections, rats were sacrificed and tumors assessed for stage, volume, location, differentiation and lymphocytic infiltrate. Embedded mucosa was assessed for dysplastic crypts. Results showed that the antagonist treatment reduced the tumor volume, staging, lymphocyte infiltrate and the number of dysplastic crypts. Thus, neurotensin(6-11)VIP(7-28) could serve as an effective cancer treatment and a preventing agent.

Animals↗
PubMedDate not supplied

Selenium interactions with carcinogens.

Although selenium was once considered to be a toxic, undesirable and carcinogenic element, it is now recognized as an essential element with anticarcinogenic properties. Epidemiological studies in the United States have shown an inverse relationship between selenium intake and certain forms of cancer in humans, but other factors must be considered since cancer is not higher in people living in selenium-deficient areas of the world (Finland, New Zealand, and Keshan disease area, China). Under most dietary conditions, selenium has been shown to reduce the spontaneous mammary tumor incidence in an inbred strain of mice. In general, selenium will counteract to various degrees, the chemical carcinogens used to produce lesions of the skin [coal tar, 3-methylcholanthrene, alpha-pyrene, and 7,12 dimethylbenz(a) anthracene (DMBA)], liver (3-methyl-4-dimethyl-aminoazobenzene, aflatoxin B1, and 2-acetylaminofluorene), mammary gland (DMBA and N-methyl-N-nitrosurea), and intestinal tract [1,2-dimethylhydrazine, bis(2-oxopropyl)nitrosamine, and azoxymethane]. Dietary factors, such as fat, will modify the protective effects of selenium. High dietary unsaturated fats, for example, markedly increase the mammary tumors in rats treated with DMBA, and selenium will reduce the tumor incidence but not to the level of rats fed a low fat diet. Other factors known to affect the anticarcinogenic effects of selenium include synthetic antioxidants, vitamin E, vitamin A and ascorbic acid. The mechanisms of selenium counteraction of carcinogens remain unknown.

9,10-Dimethyl-1,2-benzanthracene↗