Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze the influence of different levels of dietary casein on the initiation process, male Wistar rats, pair-fed on isocaloric diets containing 5, 15 or 40% casein were initiated with a single dose of aflatoxin B1, 28 days after the experimental start. From day 4 after initiation and until selection of initiated cells was started, 25 days later, rats were fed the 15% casein diet, providing an identical dietary background during the selection period. Promotion/selection of initiated cells was performed by the combined treatment with 0.02% 2-acetylaminofluorene in the 15% casein diet for 2 weeks and a two-thirds partial hepatectomy (PH) in the middle of this period. The number of enzyme-altered hepatic lesions per rat was shown to increase with increasing content of casein in the diet, both when liver sections were stained for gamma-glutamyltransferase and with immunohistochemical staining for the placental form of glutathione-S-transferase. Non-initiated rats fed the different levels of casein exhibited a very low number of foci. Livers were secured also from non-initiated rats at the same point of time as initiation was performed. Whereas no significant differences in the total microsomal content of cytochrome P450 were observed, a higher microsomal capacity to perform 16 alpha-hydroxylation of 4-androstene-3,17-dione was observed in preparations from rats fed 40% casein, when compared with rats receiving the 5% casein diet. The dietary protein content at the time of initiation did not affect the expression of the c-rasHa, c-myc or c-fos protooncogenes, either at initiation, on day 3, or at PH.
Carcinogenesis 1992 Feb
PMID:Influence of different levels of dietary casein on initiation of male rat liver carcinogenesis with a single dose of aflatoxin B1. 134 57

Previous studies in this laboratory with young Fischer 344 male rats have shown that the post-initiation development of aflatoxin B1 (AFB1)-induced gamma-glutamyltranspeptidase positive (GGT+) hepatic foci was markedly inhibited by low protein feeding, even though the energy intake was greater. This dietary effect, however, did not necessarily apply to hepatic tumor development. Thus, the present investigation was undertaken to examine this dietary effect upon the development of hepatic tumors and, is so doing, to determine the correlation of foci development with tumor development. Following AFB1 dosing (15 daily doses of 0.3 mg/kg each), animals were fed diets containing 6, 14 or 22% casein (5.2, 12.2, 19.1% protein) for 6, 12, 40, 58 and 100 weeks. Foci at 12 weeks and tumors at 40, 58 and 100 weeks developed dose-dependently to protein intake. Foci development, tumor incidence, tumor size and the number of tumors per animal were markedly reduced while the time to tumor emergence was increased with low protein feeding. Non-hepatic tumor incidence also was lower in the animals fed the lowest protein diet. Foci development indices (foci number, per cent liver volume occupied) were highly correlated with tumor incidence at 58 and 100 weeks (r = 0.90-1.00). Tumor and foci inhibition occurred in spite of the greater energy intake.
Carcinogenesis 1992 Sep
PMID:Inhibition of aflatoxin B1-induced gamma-glutamyltranspeptidase positive (GGT+) hepatic preneoplastic foci and tumors by low protein diets: evidence that altered GGT+ foci indicate neoplastic potential. 135 51

The effects of ad libitum feeding of synthetic, low-protein diets on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), on the norepinephrine concentration in the colon wall tissue and on the labelling index of colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and were given synthetic diets of equal calorie content containing 25% casein (normal-protein diet), 10% casein (low-protein diet) or 5% casein (very-low-protein diet). Administration of the low- and very-low-protein diets resulted in significant increases in the incidence and number of colon tumors at week 30. However, it did not affect the histology of the colon tumors. The low- and very-low-protein diets also resulted in significant increases in norepinephrine concentration in the proximal and distal portions of the colon wall and in the labelling indices of both parts of the colon mucosa. Our findings indicate that low- and very-low-protein diets enhance colon carcinogenesis and that this may be related to their effects in increasing the norepinephrine level in the colon wall and in stimulating proliferation of colon epithelial cells.
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PMID:Enhanced induction of colon carcinogenesis by azoxymethane in Wistar rats fed a low-protein diet. 172 1

Two 3 x 3 factorial experiments were conducted to examine the effects of dietary protein (8, 16, and 32% of energy from casein) and dietary fat (12, 24, and 48% of energy from corn oil) on the initiation and promotion of azoxymethane-induced carcinogenesis in rats. For the initiation study, 33 weanling male Sprague-Dawley rats were randomized to each of nine diets fed ad libitum. Azoxymethane was administered s.c. between the fourth to sixth weeks of feeding, providing a total dose of 6 mg/100 g body weight. All rats were subsequently fed a common diet containing 16% energy from protein and 24% energy from fat for an additional 30 to 38 weeks. For the promotion study, all rats were fed a common diet containing 16% of energy from protein and 12% of energy from fat until the completion of azoxymethane administration, when 33 rats were randomized to each of nine diets varying in fat and protein content and fed these diets until sacrifice. Low-protein diets during the initiation phase were associated with increased risk of renal adenocarcinomas (P less than 0.001) and mesenchymal (P = 0.005) malignancies. No other statistically significant relationships were found between the levels of dietary fat or protein and the prevalence of malignant lesions of the small intestine, colon, or kidney in either the initiation or promotion study (although polypoid adenocarcinoma of the colon increased suggestively from 13 to 19 to 26% of rats with increasing dietary protein during initiation). Results of a multiple logistic regression analysis, combining both studies, showed that ad libitum energy intake was significantly associated with intestinal carcinogenesis. The odds of finding an intestinal adenocarcinoma increased by 6.2 +/- 2.6% (SE) for each additional kilocalorie of mean daily ad libitum intake (P = 0.014). The quintile of rats which consumed the least averaged 60 kcal/day, while the most voracious quintile averaged 74 kcal/day. This 14 kcal/day difference in mean ad libitum intake corresponded to more than a doubling (146% increase) of the odds of developing an intestinal adenocarcinoma. These studies suggest that ad libitum energy intake is a critical factor modulating experimental colon carcinogenesis.
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PMID:The combined effects of dietary fat, protein, and energy intake on azoxymethane-induced intestinal and renal carcinogenesis. 173 47

An immunoaffinity column is described that facilitates the analysis of oxidative DNA damage. DNA adducts excised from DNA are excreted in urine and can be assayed as a measure of DNA damage in individuals. Polyclonal antibodies that recognize 8-hydroxy-2'-deoxyguanosine (oh8dG), a biomarker of oxidative damage to DNA, have been produced and their binding properties characterized. The antibodies, raised in rabbits following immunization with protein carrier-hapten conjugates prepared by covalently linking periodate-treated 8-hydroxyguanosine (oh8G) to bovine serum albumin (BSA) or casein, bind oh8dG with high affinity and selectivity, as measured by a competitive radioimmunoassay (RIA). Antibodies obtained from the rabbits immunized with the casein conjugate exhibited a binding affinity for oh8dG of 6.9 x 10(8) M-1. Studies on the relative binding affinities of these polyclonal antibodies for oh8dG, unmodified nucleosides, or derivatives of guanine indicate that the antibodies are suitable for the preparation of immunoaffinity columns that permit us to rapidly isolate oh8dG and 8-hydroxyguanine (oh8Gua) from urine. The high selectivity of the antibodies for oh8dG and oh8G reduces the amount of urinary contaminants previously observed in samples prepared by solid phase extraction, thus greatly facilitating the isolation of these damage products from urine. The relative binding affinity of these antibodies for oh8Gua and 2'-deoxyguanosine were approximately 7.6 x 10(3) and 7.4 x 10(4) fold lower respectively, than the binding affinity for oh8dG. The antibody can be used to quantitate oh8dG in enzymatic hydrolyzates of DNA with values comparable to those obtained by HPLC with electrochemical detection (HPLC-EC).
Carcinogenesis 1991 May
PMID:Immunoaffinity isolation of urinary 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanine and quantitation of 8-hydroxy-2'-deoxyguanosine in DNA by polyclonal antibodies. 202 51

The effects of ad libitum feeding of synthetic, low-protein diets on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. Rats were fed synthetic diets of equal calorie content containing 25% casein (normal protein diet), 10% casein (low-protein diet), or 5% casein (very-low-protein diet) after treatment with N-methyl-N'-nitro-N-nitrosoguanidine p.o. for 25 weeks. Administration p.o. of a very-low-protein diet containing 5% casein resulted in a significant increase in the incidence and number of gastric cancers in experimental Week 52. However, it did not affect the histology of the cancers. The very-low-protein diet also caused a significant increase in tissue norepinephrine concentration of the antral portion of the gastric wall and in the labeling index of the antral epithelial cells. These findings indicate that a very-low-protein diet enhances gastric carcinogenesis and that this effect may be related to its effect in increasing norepinephrine in the gastric wall and stimulating proliferation of antral epithelial cells.
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PMID:Enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats fed a low-protein diet. 205 88

The effect of continuous week-long administration of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) by s.c. implanted osmotic pumps was examined in male and female Syrian hamsters given access to three isocaloric synthetic diets containing 10 (LP), 20 (MP) and 30% (HP) casein respectively. At a total dose of 210 mg/kg, toxicity of HPOP, expressed as acute liver injury, was greater in male than in female hamsters. Such toxicity increased with protein intake in male, but not in female animals. Twenty-five weeks after initiation, female and male hamsters developed pancreatic ductal adenocarcinomas and to a lesser degree liver cholangiocellular and hepatocellular carcinomas. The highest incidence of pancreatic cancer was observed under HP diet regimens and was 75 and 67% in female and male hamsters respectively. Decrease of protein intake resulted in the reduction of the incidence of pancreatic cancer, which was more striking in males than in females. In males fed the MP and LP diets respectively, such an incidence declined to 33 and 6%. Although significant differences in the incidence of pancreatic cancer were not observed among female groups fed the above three diets, the multiplicity and the number of such tumors were significantly greater at the HP than the LP level. Differences in the incidence of pancreatic tumors between males and females were statistically significant only at the LP level. However, such differences were also significant at the MP level when comparisons were based on tumor number and multiplicity. Since the incidence, tumor multiplicity and size were generally greater in female than male hamsters, estrogenic hormones may play a role in the development of pancreatic ductal adenocarcinomas in this species.
Carcinogenesis 1990 Nov
PMID:Sex differences in the dietary modulation of pancreatic cancer in Syrian hamsters treated continuously with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine. 222 22

Endothelial cells produce and secrete a large number of proteases which are implicated in various disease states. These proteases fall into two classes: serine proteases include plasminogen activators (t-PA) and urokinase (u-PA) and play a major role in fibrinolysis, tissue repair and carcinogenesis; and metalloproteases include collagenases and stromelysine, two enzymes involved in the tissue remodelling that occurs during angiogenesis and tumor growth. The authors have recently identified two other proteases in porcine aortic endothelial cell culture medium. One is an elastase-like enzyme of the metalloprotease group, whereas the other is a new protease whose molecular weight is 85 Kd and whose activity becomes apparent only after exposure of the endothelial cells to platelets. The term Platelet Endothelial Cell Activated Protease accurately describes this enzyme. PECAP degrades casein and fibrinogen. Because PECAP is not inhibited by the usual inhibitors of the various classes of proteases, it remains at present unclassified.
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PMID:[Endothelial cell proteases and their modulation by platelets]. 229 Jun 90

Neoplastic development in the rat mammary gland can be suppressed by inhibition of the activity of several enzymes involved in eicosanoid biosynthesis. In order to investigate the potential utility of prostacyclin and thromboxane synthetases as targets for mammary cancer chemoprevention, experiments were conducted to determine the influence of tranylcypromine (TCP), an inhibitor of prostacyclin synthetase, and imidazole (IMI), an inhibitor of thromboxane synthetase, on mammary carcinogenesis induced in rats by N-methyl-N-nitrosourea. Fifty-day-old female Sprague-Dawley [Hsd:SD(BR)] rats received a single s.c. dose of 0 or 40 mg of N-methyl-N-nitrosourea per kg of body weight. Beginning 7 days after carcinogen administration, groups of rats were fed isoenergetic, casein-based diets containing 3 or 20% corn oil (w/w), supplemented with (per kg of diet) 10 mg of TCP, 1000 mg of IMI, or sucrose carrier only. TCP reduced mammary carcinoma multiplicity in rats fed the 20% corn oil diet, but had no effect in rats fed the diet containing 3% fat. By contrast, supplementation with IMI increased mammary cancer incidence in the group fed the 20% fat diet and increased carcinoma multiplicity in the 3% fat group to the levels seen in rats fed the 20% fat diet. These data suggest that inhibition of prostacyclin synthetase, but not thromboxane synthetase, may present a useful mechanism for mammary cancer chemoprevention in animals consuming a diet high in fat. Furthermore, the differential effects of TCP and IMI in rats fed low and high fat diets suggest that the action of dietary fat in mammary cancer induction may involve influences on the arachidonic acid cascade.
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PMID:Differential effects of tranylcypromine and imidazole on mammary carcinogenesis in rats fed low and high fat diets. 249 73

The effects of selenium intake on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis were examined in rats fed a diet high in mixed fats and representative of that consumed in North America. Six groups of 20 rats were fed an AIN-76 diet modified to contain 20% fat from lard:corn oil (3:1 wt/wt) and various amounts of selenium (0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet). At wk 5, animals in groups 2-6 were dosed with 4.32 mg of DMBA. Serum clinical parameters and the activities of plasma selenium-dependent and total glutathione peroxidase (GSHPx), erythrocyte GSHPx and superoxide dismutase (SOD) were determined every 4 wk for 25 wk. The extent of lipid peroxidation was determined by measuring urinary malondialdehyde during wk 13 and 24, and erythrocyte malondialdehyde at wk 25. Erythrocyte GSHPx was found to be a better indicator of selenium status than plasma activity, while SOD did not vary with dietary selenium. The group of animals fed 4.0 mg Se/kg diet had reduced numbers of tumors (P less than 0.01), but this reduction was associated with evidence of chronic selenium toxicity. Variations in GSHPx activity with dietary selenium did not result in differences in tumor incidence, nor in changes in lipid peroxidation in the other groups. Thus, nontoxic levels of selenium do not appear to offer any protective effect during carcinogenesis in rats fed a casein-based diet similar in fat content to that consumed by North Americans.
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PMID:Effects of dietary selenium on DMBA-induced carcinogenesis in rats fed a diet high in mixed fats. 249 71


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