摘要:

AbstractWe evaluated the effect of dietary cholesterol and oxidized cholesterol on the promotion of aberrant crypt foci (ACF), which are putative precancerous lesions in the colon. Sixty female C57BL/6J mice were given four weekly injections (ip) of azoxymethane (AOM) then fed either a control AIN‐76 diet or the control diet supplemented with 0.3% cholesterol or 0.3% oxidized cholesterol for 100 days. The oxidized cholesterol was prepared by heating cholesterol at 110°C for 48 hours. Gas chromatographic analysis of the oxidized cholesterol showed that 96% of the cholesterol was unchanged and less than 2% of the cholesterol was oxidized. The remaining 2% impurities were unidentified and present in both the cholesterol and heated cholesterol. The number of ACF in the group fed cholesterol was significantly lower than the control group (7.9±1.0 vs. 12.5±1.2, p<0.01). The number of ACF in the group fed oxidized cholesterol (10.1±1.1) was not different from the control or cholesterol groups. The size of the ACF (no. of crypts per focus) did not differ between the three dietary groups. Serum low‐density lipoprotein (LDL) cholesterol was greater in the cholesterol‐fed group than the control group (40.5±4.6 vs. 24.3±3.6 mg/dl, p<0.05). LDL cholesterol from the animals fed oxidized cholesterol (37.7 + 4.7 mg/dl) was not different from the control or cholesterol‐fed animals. Total and high‐density lipoprotein (HDL) cholesterol did not differ between the groups. The results show that dietary cholesterol significantly inhibits the promotion of ACF in the colon. The elevated LDL cholesterol may inhibit de novo cholesterol synthesis in the preneoplastic colonic epithelial cells, thereby inhibiting DNA synthesis and cell proliferation.

ISSN:0163-5581    

DOI:10.1080/01635589609514433

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractThe ability of dietary antioxidants to reduce lipid peroxidation induced by iron overload was examined in weanling male Sprague‐Dawley rats. Animals were fed ad libitum a modified AIN‐76A diet (control) or control diet with 0.5%α‐tocopherol acid succinate, 0.5% crystalline trans‐β‐carotene, or 0.5%α‐tocopherol acid succinate + 0.5% trans‐β‐carotene for four weeks. In the following four‐week period, the animals received the above diets with 10,000μg Fe/g; a control group continued to receive 35μg Fe/g, and a high‐iron group received 10,000μg Fe/g with no antioxidants. After four weeks of dietary supplementation withα‐tocopherol,β‐carotene, orα‐tocopherol +β‐carotene, liver concentrations ofα‐tocopherol andβ‐carotene increased significantly (p<0.001). Liver lipid peroxidation, measured by the lipid‐conjugated diene assay, increased significantly from 0.012μmol/mg of lipid in the controls to 0.021μmol/mg of lipid in animals receiving the high‐iron diet. However, lipid peroxidation was significantly reduced in all animals fed the antioxidants, with the group fedα‐tocopherol +β‐carotene having a lower level than the high‐iron group. Total serum cholesterol was elevated in animals fed a high‐iron diet and in animals fed the high‐iron diet withα‐tocopherol. In contrast, total serum cholesterol levels in the two groups of animals receiving the diets containing high iron withβ‐carotene alone or high iron withβ‐carotene +α‐tocopherol were significantly reduced to the level of the control group. High‐density lipoprotein cholesterol also decreased to baseline in the animals receivingβ‐carotene alone. Modulation of lipid peroxidation byα‐tocopherol orβ‐carotene may be an important mechanism for reducing oxidative stress.

ISSN:0163-5581    

DOI:10.1080/01635589609514434

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractCarcinogen induction of neoplasms in rodent colon has been used as a model for human colon cancer development and for evaluating chemopreventive regimens. We studied the regional distribution of small and large intestinal tumors in 229 rats given azoxymethane (AOM) once weekly for two weeks (15 mg/kg sc). The AOM regimen induced 63% more tumors in distal (DC) than in proximal colon (PC), although tumor volume was greater in PC. A high‐fat (23% com oil) diet increased tumors in PC and DC (p<0.01). Caloric restriction of 10–30% of the ad libitum diet progressively reduced DC tumor formation but did not alter PC tumors. Tumor volume was unaffected by either regimen. Small intestinal tumors were concentrated in the proximal 15 cm of the intestine and were unaffected by dietary manipulation. This AOM model of colon tumor formation approximates human colon cancer distribution and is an appropriate model for rodent chemopreventive studies.

ISSN:0163-5581    

DOI:10.1080/01635589609514435

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractRRR‐α‐tocopheryl succinate (VES) was studied for effects on murine EL‐4 cell proliferation and production of interleukin‐2 (IL‐2) and transforming growth factor‐β(TGF‐β). VES was biphasic in its actions: 0.1μg/ml enhanced EL‐4 cell proliferation, whereas 10–20μg/ml inhibited cellular proliferation. Cell‐conditioned media (CM) from EL‐4 cells treated with 0.2 ng/ml phorbol myristate acetate (PMA) + 0.1μg/ml VES contained increased amounts of IL‐2, as determined by the murine cytotoxic ? cell IL‐2‐dependent CTLL‐2 bioassay. VES at 0.1μg/ml or 0.1μg/ml VES + 0.2 ng/ml PMA induced the expression of IL‐2 mRNA by EL‐4 cells three to nine hours after treatment. CM from EL‐4 cells treated with VES at 10–20μg/ml exhibited potent antiproliferative activity when tested in the TGF‐β‐responsive mink lung cell (Mv1Lu) bioassay and showed reduced inhibitory effects when tested on TGF‐βreceptor‐negative mink lung (DRA‐27) cells. CM from control‐treated EL‐4 cells exhibited no antiproliferative activity. The VES‐induced antiproliferative activity was characterized as TGF‐βby neutralization analyses and immunoprecipitation of metabolically labeled proteins with TGF‐β‐specific reagents. VES treatment of EL‐4 cells had no effect on TGF‐β1mRNA expression while downregulating TGF‐β3mRNA expression. In summary, these studies showed that 0.1μg/ml VES enhanced cellular proliferation, in part, via increased IL‐2 production, whereas 10–20μg/ml VES inhibited cellular proliferation, in part, via the secretion of biologically active TGF‐β.

ISSN:0163-5581    

DOI:10.1080/01635589609514436

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractFemale Sprague‐Dawley rats (n = 270) were randomly divided into nine subgroups (30 rats/group) and fed diets with fat contents ranging from 5% to 45% of total energy, in which fat was isocalorically substituted for carbohydrates. At Week 3, the rats were given a single injection of methylnitrosourea (MNU, 50 mg/kg body wt). At Weeks 4 and 5, rats were given an injection of azoxymethane (AOM, 15 mg/kg body wt sc). The rats were maintained on their respective experimental diets until they were sacrificed. Nine weeks after the injection of MNU, 10 rats from each group were killed and their mammary tissue was examined for tumors and their colons for aberrant crypt foci (ACF) formation. The results showed no significant increase in the number of colonic ACF or mammary tumors at 11 weeks among individual groups consuming 5–25% energy from fat or among groups consuming 30–45% energy from fat. Data analysis indicated that the effects of the two diets (5–25% energy from fat and 30–45% energy from fat) on ACF formation as well mammary tumor development were statistically different. Continuation of the diets for 32 weeks led to the development of colonic and mammary tumors. Analysis of the combined group tumor incidence data clearly showed that the colonic and mammary tumor incidence in groups fed 30–45% of energy from fat was significantly higher than that observed among groups fed 5–25% of energy from fat. Linear regression analysis of the colonic ACF at 11 weeks, colonic tumor incidence at 32 weeks, and mammary tumor incidence at 11 and 32 weeks showed good linear correlation, demonstrating the potential value of ACF and mammary tumors at 11 weeks for evaluating the carcinogenic risk associated with different diets. The main conclusion of the experiment is that the incidence of colon and mammary cancers increased rapidly when the dietary levels of fat were increased from 15% to 30% of calories and that there was no significant influence on the colon and mammary cancer risk beyond 30% of calories from fat.

ISSN:0163-5581    

DOI:10.1080/01635589609514437

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractThe relationship between dietary fat intake (level and type) and the development of breast cancer in humans is a matter of concern in Western society. A high fat intake is associated with a greater mammary cancer risk in humans and in animal models. Higher intake of polyunsaturated fatty acids in humans shows little or no association with mammary tumor development in epidemiologic surveys. From literature data, it appears that a higher intake of polyunsaturated fatty acids (linoleic acid) is related to an increase in mammary tumorigenesis in animal studies in which chemical carcinogens like dimethylbenz[a]anthracene are used as tumor initiator. Mostly the latency period in these chemically induced models is rather short. In this study, the Balb/c‐MMTV (mouse mammary tumor virus) mouse strain was chosen as an animal model: MMTV leads to tumor initiation, and dietary factors influence tumor promotion over a relatively long latency period. The mice were fed diets with two fat concentrations: a high [36% of energy (en%)] or low (16 en%) fat level; fat was isocalorically replaced by carbohydrates (cornstarch). At both dietary fat levels, linoleic acid was given at four levels: 2, 3, 6, and 10 en%. Linoleic acid‐rich fat was isocalorically replaced by oleic acid‐rich fat. The diets were consumed ad libitum over a lifetime. Animals were euthanized as soon as mammary tumor diameter was≥1 cm or when the animals were in a poor clinical condition. The incidence of mammary tumors at 18 months was significantly higher in one group only: 36 en% fat and 2 en% linoleic acid. This group also showed the shortest mean latency period for mammary tumor development. Mean mammary tumor incidence was higher and mean onset time shorter in the four high‐fat groups than in the low‐fat groups. No (linear) dose‐response relationship between dietary linoleic acid concentration and mammary tumor incidence and latency period was observed. This indicates that a higher dietary linoleic acid intake does not increase the incidence or shorten the latency period of breast cancer in the Balb/c‐MMTV mouse strain at two different dietary fat levels.

ISSN:0163-5581    

DOI:10.1080/01635589609514438

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractLevels of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the breast and uterine cervix were compared with levels in healthy controls and patients with benign diseases of the breast and cervix. Serum ascorbate levels were significantly lower in patients with benign diseases of the breast and cervix than in controls. In cancer patients, there was a significant trend of lower serum vitamin levels with increasing stage of the disease.

ISSN:0163-5581    

DOI:10.1080/01635589609514439

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractTo study the effect of dietary sugars and starches on parameters linked to colon carcinogenesis, female Sprague‐Dawley rats were fed for one month five different diets containing sucrose, glucose, fructose, cornstarch, or Hylon 7, a starch with a high amylose content. After this period, colon proliferation, assessed by [3H]thymidine incorporation in vitro, was higher (p<0.05) in rats fed sucrose than in rats fed glucose, fructose, or cornstarch [labeling index was 7.17±0.75, 5.03±0.70, 4.55±0.72, 4.00±0.70, and 5.89±1.05 (SE) in sucrose, glucose, fructose, cornstarch, and Hylon 7 diets, respectively]. Cecal pH was lower in rats fed cornstarch and Hylon 7 than in rats fed sucrose, glucose, or fructose. Content of short‐chain fatty acids (SCFAs) in the cecum was higher in rats fed Hylon 7 than in those fed glucose and fructose. In conclusion, glucose and fructose, compared with sucrose, decrease mucosal proliferation and may be considered protective factors in colon carcinogenesis, although they do not affect SCFA production and cecal pH. On the contrary, Hylon 7 does not change mucosal proliferation but increases SCFAs and lowers cecal pH, two conditions associated with a lower risk of colon cancer.

ISSN:0163-5581    

DOI:10.1080/01635589609514440

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractColonic mucosal proliferation, aberrant crypt foci (ACF) induction, and fecal bile acids, parameters connected to the risk of colon cancer development, were studied in female F344 rats treated with starch or sucrose boluses or with a sucrose diet.Cell proliferation was higher in animals treated with a single sucrose bolus than in those given a starch bolus (15 g/kg body wt), with 4.3±0.64 and 2.17±0.57 (SE) mitotic figures (MF) per crypt in the sucrose and starch bolus groups, respectively (p<0.01). When azoxymethane (AOM, 20 mg/kg) was administered 24 hours after a single sucrose or starch bolus, the number of ACF per colon after 30 days was higher in the sucrose bolus group [107.5±9.5 (SE)] than in the starch bolus group (67.8±0.9, p<0.01). In additional experiments, colon cell proliferation (MF/crypt) was higher in rats given boluses of sucrose three times per week for 40 days after AOM (20 mg/kg) [5.9±0.7 (SE)] than in rats given starch boluses (2.96±0.4) or fed sucrose continuously (3.6±0.5). On the contrary, after 40 days of dietary treatment, the number, dimension, and percentage of ACF secreting sulfomucins and sialomucins were not varied among these three groups. However, the percentage of“large ACF”(ACF with≥4 crypts) secreting sialomucins or predominantly sialomucins was higher (p<0.05) in the sucrose bolus group than in the starch group. The concentration of fecal bile acids and long‐chain fatty acids was the same in the sucrose and starch groups, but the concentrations of deoxycholic and oleic acid were significantly higher in the sucrose bolus group. In conclusion, the administration of sucrose as a bolus had a stronger effect than continuous sucrose feeding on some parameters related to colon carcinogenesis and might be considered a risk factor in colon carcinogenesis.

ISSN:0163-5581    

DOI:10.1080/01635589609514441

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractMale Fischer 344 rats were fed a 20% or a 5% corn oil diet and were injected subcutaneously with dimethylhydrazine (DMH) weekly for 16 weeks. In addition, an approximately equal number of animals challenged with DMH were fed daily, until the end of the study, 2×1010Lactobacillus casei subsp. rhamnosus strain GG starting three weeks before DMH administration or after the ninth weekly injection. The feeding of the Lactobacillus GG before and during carcinogen treatment resulted in a significant decrease in the incidence of colon tumors and the number of small intestinal and colon tumors per tumor‐bearing animal for rats fed a 20% corn oil diet. This decrease in tumor incidence or number of tumors was not seen when animals were fed the Lactobacillus after the ninth week of carcinogen treatment. Animals fed a 5% corn oil diet had a lower tumor incidence and number of tumors resulting from the decrease in dietary fat; in addition the feeding of Lactobacillus GG before the carcinogen challenge resulted in a lower incidence of colon tumors. These studies show that a specific strain of L. casei subsp. rhamnosus designated GG can interfere with the initiation or early promotional stages of DMH‐induced intestinal tumorigenesis, and this effect is most pronounced for animals fed a high‐fat diet.

ISSN:0163-5581    

DOI:10.1080/01635589609514442

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor