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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.
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PMID:Garlic and associated allyl sulfur components inhibit N-methyl-N-nitrosourea induced rat mammary carcinogenesis. 860 70

The reason for different phosphorylation of topoisomerase I in two sublines of L5178Y murine lymphoma (LY cells) was investigated. Camptothecin-resistant LY-S cells show increased poly(ADP-ribose) level and lowered topoisomerase I phosphorylation compared to camptothecin-sensitive LY-R cells. In this study diminished phosphorylation of LY-S topoisomerase I was observed for sites recognized by casein kinase 2 but not for those phosphorylated by protein kinase C. Tryptic digests of LY-S topoisomerase I labeled in vitro by casein kinase 2 indicated that phosphorylation was similarly lowered at different sites. Activity of casein kinase 2 measured in nuclear extracts was about 1.7 times lower for LY-S than LY-R cells. This difference was diminished or eliminated by increasing casein concentration, diluting the extract or increasing the ionic strength. Activity of poly(ADP-ribose) polymerase was 5.3 times higher in LY-S than in LY-R nuclei. When the activity of the polymerase was inhibited by treatment of LY-S cells with benzamide, casein kinase 2-catalyzed phosphorylation of topoisomerase I increased. This was accompanied by an increase in sensitivity to camptothecin as reflected in the diminished viability of LY-S cells.
Carcinogenesis 1996 Mar
PMID:Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism. 863 Nov 20

Significant alarm has existed among the general public in the past few years that eating red meat may cause human colon cancer. Iron in beef has been hypothesized as one of the factors in the etiology of this cancer. The present study was designed to test the hypothesis that dietary iron solely from beef would enhance colon tumorigenesis induced in rats. Tumors were induced in Sprague-Dawley rats with 1,2-dimethylhydrazine (20 mg/kg body weight for 10 weeks). Seventy male weanling rats were randomized to two dietary treatment groups with two iron sources (very lean beef vs. iron citrate) as the factor. The rats were allowed free access to the respective diet and deionized water for 27 weeks. At termination of the study, the rats were examined for location, size and type of colon or extracolonic lesions. No significant differences were found in total incidence and number of colon tumors between the beef (51.7%, 0.8 tumors/rat) and casein (62.1%, 0.9 tumors/rat) diets, although the serum iron levels of rats fed the beef diet were higher than for those fed the casein diet. The results demonstrate that, when lean beef is used as an iron source, the risk for colon carcinogenesis is not increased.
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PMID:Non-promoting effects of iron from beef in the rat colon carcinogenesis model. 902 73

The effect of a purified, high protein diet on enhanced gastric carcinogenesis induced by oral administration of NaCl was investigated in Wistar rats. Rats were fed on a purified diet with an equalized caloric content, containing 8% NaCl and 25% casein (normal protein diet), or 50% casein (high protein diet) after oral treatment with N-methyl-N'-nitro-N-nitrosoguanidine for 25 weeks. In week 52, oral administration of NaCl had significantly increased the incidence and size of gastric cancer in rats fed a normal protein diet. However, NaCl had no significant effect on gastric carcinogenesis in rats fed a high protein diet. Oral administration of NaCl also caused a significant increase in tissue norepinephrine concentrations in the antral portion of the gastric wall, and increased the labeling indices of the antral epithelial cells of rats fed on a normal protein diet. However, in rats fed a high protein diet, administration of NaCl had no significant influence on these two parameters. These findings indicate that a high protein diet attenuates enhanced gastric carcinogenesis induced by the administration of NaCl, and that this effect may be related to its ability to decrease norepinephrine concentrations in the gastric wall, which subsequently decreases the proliferation of antral epithelial cells.
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PMID:Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet. 921 70

Epidemiological studies show a low incidence of colon cancer in many Latin American countries where the consumption of dry beans (e.g., pinto) is high. The purpose of this study was to use rats as an animal model to obtain experimental data on the inhibition of colon carcinogenesis by dry beans. Fifty-three 5-wk-old weanling male F344 rats were randomly assigned by weight to the following groups: control (11 rats), casein diet (21 rats), and bean diet (21 rats). Animals fed the casein and bean diets were treated with the carcinogen azoxymethane (AOM) once weekly for 2 wk. Rats in the control group also consumed the casein diet but were not exposed to AOM. All diets were isocaloric. The protein concentration of the diets was adjusted to 18 g/100 g with casein, and the fat concentration was adjusted to 5 g/100 g with corn oil. Rats fed the bean diet had significantly fewer colon adenocarcinomas (P < 0.05) than rats fed the casein diet (5 vs. 22 tumors), and significantly fewer rats fed the bean diet (P < 0.05) had colonic tumors than did casein-fed rats (24 vs. 50%). Tumor multiplicity was also significantly lower for the bean-fed rats, and significantly fewer (P < 0.05) tumors per tumor-bearing rat were observed in bean-fed rats than in casein-fed rats (1.0 +/- 0.0 vs. 2.5 +/- 0.6). This study demonstrates that dry beans contain anticarcinogenic compounds capable of inhibiting AOM-induced colon cancer in rats. However, the specific anticarcinogenic components within dry beans have not been identified, and it is unclear whether dietary fiber, phytochemicals or other components within dry beans are primarily responsible for the anticarcinogenic properties of beans.
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PMID:Dry beans inhibit azoxymethane-induced colon carcinogenesis in F344 rats. 940 82

Results of recent studies in animal models of mammary carcinogenesis showed that the soybean isoflavone genistein is a chemopreventive agent. The objective of the present study was to determine whether soybean isoflavones can be used for the prevention of human breast carcinogenesis. Human adenocarcinoma cells that are either estrogen-receptor positive (such as MCF-7) or estrogen-receptor negative (such as MDA-MB-468) were used as our model system. Treatment of these cells with genistein concentrations of 15, 30, and 45 micromol/L resulted in cell growth inhibition, which was accompanied by the expression of maturation markers. Maturation was monitored by the induction of intracytoplasmic casein and lipids and the membrane protein intercellular adhesion molecule-1. These maturation markers were optimally expressed after 9 d of treatment with 30 mmol genistein/L. Both estrogen receptor-positive and -negative cells became differentiated in response to genistein treatments, suggesting that the antiestrogenic function of genistein is unrelated to the mechanism of cell differentiation. Daidzein, the other major isoflavone component of soybeans, did not induce differentiation in either MCF-7 or MDA-MB-468 cells. To explore the potential applications of this result, we used the nude mouse xenograft model of carcinogenesis. Treatment of either cell line with genistein before implantation into nude mice diminished the cells' tumorigenic potential. These data suggest that initiation of the differentiation program provides a protective effect against tumor growth in mouse xenografts.
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PMID:Genistein induces maturation of cultured human breast cancer cells and prevents tumor growth in nude mice. 984 11

High intake of red meat or processed meat is associated with increased risk of colon cancer. In contrast, consumption of white meat (chicken) is not associated with risk and might even reduce the occurrence of colorectal cancer. We speculated that a diet containing beef or bacon would increase and a diet containing chicken would decrease colon carcinogenesis in rats. One hundred female Fischer 344 rats were given a single injection of azoxymethane (20 mg/kg i.p.), then randomized to 10 different AIN-76-based diets. Five diets were adjusted to 14% fat and 23% protein and five other diets to 28% fat and 40% protein. Fat and protein were supplied by 1) lard and casein, 2) olive oil and casein, 3) beef, 4) chicken with skin, and 5) bacon. Meat diets contained 30% or 60% freeze-dried fried meat. The diets were given ad libitum for 100 days, then colon tumor promotion was assessed by the multiplicity of aberrant crypt foci [number of crypts per aberrant crypt focus (ACF)]. The ACF multiplicity was nearly the same in all groups, except bacon-fed rats, with no effect of fat and protein level or source (p = 0.7 between 8 groups by analysis of variance). In contrast, compared with lard- and casein-fed controls, the ACF multiplicity was reduced by 12% in rats fed a diet with 30% bacon and by 20% in rats fed a diet with 60% bacon (p < 0.001). The water intake was higher in bacon-fed rats than in controls (p < 0.0001). The concentrations of iron and bile acids in fecal water and total fatty acids in feces changed with diet, but there was no correlation between these concentrations and the ACF multiplicity. Thus the hypothesis that colonic iron, bile acids, or total fatty acids can promote colon tumors is not supported by this study. The results suggest that, in rats, beef does not promote the growth of ACF and chicken does not protect against colon carcinogenesis. A bacon-based diet appears to protect against carcinogenesis, perhaps because bacon contains 5% NaCl and increased the rats' water intake.
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PMID:Effect of meat (beef, chicken, and bacon) on rat colon carcinogenesis. 1005 Feb 67

Mammary epithelial organoids (MEO), isolated from pubescent rats, were cultured within a reconstituted basement membrane in transwell inserts, in the presence or absence of mature mammary adipocytes in the lower well. This system allowed for free medium exchange between the two compartments, without direct cell-to-cell contact. When cultured in serum-free medium supplemented with insulin, prolactin, hydrocortisone, progesterone, and various epidermal growth factor (EGF) concentrations, mammary adipocytes did not affect epithelial cell growth, but enhanced epithelial differentiation. Casein and lipid accumulations were monitored as indicators of functional differentiation of MEO. Mammary adipocytes significantly enhanced casein and lipid accumulation within the MEO, independently of EGF concentration. Furthermore, adipocytes induced MEO to preferentially undergo alveolar morphogenesis, inhibited squamous outgrowth, and increased lumen size. These findings demonstrate that morphological and functional differentiation of mammary epithelial cells is profoundly enhanced by the adipose stroma and that these effects are mediated by diffusible paracrine factors. This new model can be exploited in future studies to define the mechanisms whereby hormones and growth factors regulate mammary gland development and carcinogenesis. Moreover, it could complement in vivo reconstitution/transplantation studies, which are currently employed to evaluate the role of specific gene deletions in the regulation of mammary development.
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PMID:Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells. 1006 68

Dietary glycine inhibited hepatocyte proliferation in response to the carcinogen WY-14,643. Since increased cell replication is associated with hepatic cancer caused by WY-14,643, glycine may have anti-cancer properties. Therefore, these experiments were designed to test the hypothesis that dietary glycine would inhibit the growth of tumors arising from B16 melanoma cells implanted subcutaneously in mice. C57BL/6 mice were fed diet supplemented with 5% glycine and 15% casein or control diet (20% casein) for 3 days prior to subcutaneous implantation of B16 tumor cells. Tumor volume was estimated from tumor diameter for 14 days. Tumors were excised, weighed and sectioned for histology post-mortem. B16 cells and endothelial cells were cultured in vitro to assess effects of glycine on cell growth. Statistical tests were two-sided and a P-value of 0.05 was defined as a significant difference between groups. Weight gain did not differ between mice fed control and glycine-containing diets. B16 tumors grew rapidly in mice fed control diet; however, in mice fed glycine diet, tumor size was 50-75% less. At the time of death, tumors from glycine-fed mice weighed nearly 65% less than tumors from mice fed control diet (P < 0.05). Glycine (0.01-10 mM) did not effect growth rates of B16 cells in vitro. Moreover, tumor volume and mitotic index of B16 tumors in vivo did not differ 2 days after implantation when tumors were small enough to be independent of vascularization. After 14 days, tumors from mice fed dietary glycine had 70% fewer arteries (P < 0.05). Furthermore, glycine (0.01-10 mM) inhibited the growth of endothelial cells in vitro in a dose-dependent manner (P < 0.05; IC50 = 0.05 mM). These data support the hypothesis that dietary glycine prevents tumor growth in vivo by inhibiting angiogenesis through mechanisms involving inhibition of endothelial cell proliferation.
Carcinogenesis 1999 May
PMID:Dietary glycine inhibits the growth of B16 melanoma tumors in mice. 1033 95

Sodium chloride (NaCl) initiates and promotes experimental carcinogenesis in rats. We recently found that a high-protein diet attenuates NaCl-enhanced gastric carcinogenesis in Wistar rats. To investigate the effect of a purified low-protein diet on NaCl-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, rats were fed a purified diet with an equalized caloric content containing 1% or 2% NaCl and 25% casein (normal-protein diet) or 10% casein (low-protein diet) after oral treatment with MNNG for 25 weeks. In week 52, neither 1% nor 2% NaCl had a significant effect on gastric carcinogenesis in rats fed a normal-protein diet. However, oral administration of 2%, but not 1%, NaCl significantly increased the incidence of gastric cancers in rats fed a low-protein diet. Oral administration of 2% NaCl also significantly increased the bromodeoxyuridine (BrdU)-labeling index and the ornithine decarboxylase (ODC) activity and decreased apoptosis of gastric cancers in rats fed a low-protein diet. However, 2% NaCl had no significant effect on these three parameters in rats fed a normal-protein diet. These findings indicate that a low-protein diet enhances the effect of NaCl in gastric carcinogenesis and that this enhancement may be mediated by increased cell proliferation and reduced apoptosis of gastric cancers.
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PMID:Low-protein diet promotes sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 1045 51


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