摘要:

AbstractDietary administration of the soybean isoflavone genistein (50 and 250 ppm) for 30 days significantly increases the activities of antioxidant enzymes in various organs of SENCAR mice. Feeding a 250‐ppm genistein diet to SENCAR mice significantly increases the activities of catalase in small intestine, liver, and kidney, the activities of superoxide dismutase and glutathione peroxidase in skin, and the activity of glutathione reductase in skin and small intestine. Feeding 50 ppm genistein to SENCAR mice results in elevated catalase activity in the small intestine and increases glutathione‐S‐transferase activities in skin, small intestine, liver, kidney, and lung. Dietary genistein s greatest enhancement of antioxidant enzyme activities occurred in skin and small intestine. Our results suggest that dietary genistein enhances the activities of antioxidant enzymes in various organs, which may be a mechanism(s) of genistein's chemopreventive action.

ISSN:0163-5581    

DOI:10.1080/01635589609514423

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractThe RRR‐α‐tocopheryl succinate form of vitamin ? [vitamin ? succinate (VES)] inhibits the proliferation of avian reticuloendotheliosis virus‐transformed RECC‐UTC4–1 (C4–1) lymphoblastoid cells in a dose‐dependent manner, blocks the cells in the G2IM cell cycle phase, and induces the cells to undergo apoptosis. Apoptosis was documented by demonstrating changes that are characteristic of this type of cell death, including morphological analyses of chromatin condensation by 4’,6‐diamidine‐2'‐phenylindole dihydrochloride (DAPI) staining using scanning confocal and traditional fluorescent microscopy; flow cytometry analyses of propidium iodide‐labeled DNA showing fragmented DNA as a pre‐G1 peak; two‐color flow cytometry analyses of intact cells labeled first by the TUNEL procedure (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick‐end‐labeled DNA stained with fluorescein isothiocyanate‐labeled avidin) and then by propidium iodide demonstrating fragmented DNA; and electrophoresis of DNA showing a DNA ladder created by internucleosomal DNA fragmentation. The percentage of apoptotic cells was determined by DAPI staining and showed 11%, 27%, and 49% of cells to be apoptotic after treatment with 10μg/ml VES for one, two, and three days, respectively. Analyses of mRNA levels of genes that have been implicated in the apoptotic process, namely, bcl‐2, c‐myc, and c‐jun, revealed no change in bcl‐2, decreases in c‐myc mRNA levels after 36 hours of treatment, and increases in c‐jun mRNA levels within four hours after treatment. Western immunoblotting analyses of protein levels for the transcription factors c‐Myc and c‐Jun showed normal levels of c‐Myc at early time points and decreased levels at 24 and 48 hours after treatment. c‐Jun increased as early as 6 hours after treatment and returned to lower (yet still elevated over control) levels by 48 hours. To determine possible functional consequences of increased c‐Jun expression, gel electrophoretic mobility assays were conducted that showed increased AP‐1 binding at 24 and 48 hours after treatment. These data show that VES induces apoptosis in reticuloendotheliosis virus‐transformed lymphoid cells and suggest that decreases of c‐Myc protein and increases of c‐Jun protein and DNA binding capacity may be playing a role in VES‐mediated events leading to apoptosis in this cell type.

ISSN:0163-5581    

DOI:10.1080/01635589609514424

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractTo test whetherβ‐carotene or canthaxanthin can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) in a sequential protocol of hepatocarcinogenesis, for three weeks male weanling rats were fed diets containingβ‐carotene or canthaxanthin (300 mg/kg diet) or excess vitamin A (70,000 IU/kg diet) or were givenβ‐carotene by injection (9 injections at 10 mg/kg body wt ip). On Day 15, all rats were injected with 200 mg DEN/kg body wt ip; later they were submitted to 2‐acetylaminofluorene treatment and to two‐thirds hepatectomy, then to phenobarbital treatment, after whichγ‐glutamyltranspeptidase‐and placental glutathione‐S‐transferase‐positive liver foci were histologically detected. Neitherβ‐carotene (fed or injected), canthaxanthin, nor an excess of dietary vitamin A had an influence on the number and size of preneoplastic liver foci, despite a significant incorporation and persistence in liver of both carotenoids, especially canthaxanthin, and of supplemental vitamin A. These results are in conflict with another report in whichβ‐carotene, given to rats during the initiation phase, was found to strongly inhibit DEN‐induced hepatocarcinogenesis.

ISSN:0163-5581    

DOI:10.1080/01635589609514425

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractA number of studies have demonstrated the protective effect of dietary calcium against risk for colon cancer. The objective of this experimental study was to test the efficacy of two sources of dietary calcium, elemental calcium in the form of CaCO3and dairy calcium as nonfat dried milk (NFDM), in colon tumor inhibition. Male weanling F344 rats were fed six test diets containing low (LF, 5%) and high (HF, 20%) levels of com oil and low (0.5%) and high (1.0%) levels of calcium supplemented as CaCO3or NFDM in a 2×3 factorial design. Tumors were induced with two weekly injections of azoxymethane at 12 mg/kg body wt. After 27 weeks on the test diets, animals were necropsied for tumor analysis. There was no difference in tumor incidence for fat or calcium source main effects, but a significant interaction was seen between fat and calcium source, with the lowest tumor incidence seen in the HF/NFDM group. Calcium compartmentalization studies demonstrated no effects of calcium on serum calcium levels but increased urinary and fecal water calcium in the higher‐calcium diets. Increased dietary calcium also decreased fecal bile acid concentrations, but there was no effect on fecal water bile acids. Intermediate biomarkers of colon carcinogenesis were not affected by the dietary treatments except for fat effects on carcinogen‐induced nuclear aberrations. These results indicate that source of calcium is not critical but that total dietary context may affect efficacy of calcium against colon carcinogenesis.

ISSN:0163-5581    

DOI:10.1080/01635589609514426

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractCancer chemotherapy frequently fails, because tumors develop multiple drug resistance (MDR). Pharmacological efforts to reverse this MDR phenotype and sensitize resistant tumor cells have utilized verapamil (VER) to inhibit p‐glycoprotein function and buthionine sulfoximine (BSO) to inhibit glutathione synthesis. Our previous results indicate that restriction of two amino acids, tyrosine (Tyr) and phenylalanine (Phe), may potentially suppress the MDR phenotype. These results show that in vivo Tyr and Phe restriction improves the therapeutic response of a metastatic variant of B16‐BL6 (BL6) murine melanoma to adriamycin (ADR) and B16 melanoma to levodopa methyl ester. We examine whether in vitro limitation of Tyr and Phe suppresses ADR resistance of BL6 cells and whether Tyr‐Phe modulation of the MDR phenotype is applicable to other tumor types, particularly P388 murine leukemia. Mechanisms underlying Tyr‐Phe modulation of ADR resistance are examined in the presence of VER and BSO, singly and in combination. Our results indicate that in vitro Tyr and Phe restriction has no effect on BL6 resistance to ADR However, Tyr and Phe restriction does increase the sensitivity of ADR‐resistant P388 cells to ADR without affecting drug efflux, ADR uptake, or glutathione levels. In addition, this enhanced ADR sensitivity of P388 cells is even more pronounced in the presence of BSO. Suppression of ADR resistance in P388‐resistant cells by Tyr and Phe restriction indicates that Tyr‐and Phe‐mediated modulation of the MDR phenotype is possible and that Tyr and Phe restriction may be useful as a potential adjuvant to effective cancer chemotherapy.

ISSN:0163-5581    

DOI:10.1080/01635589609514427

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractThe anti‐initiating properties of allyl sulfides on rat liver carcinogenesis induced by N‐nitroso‐diethylamine (NDEA) or aflatoxin B1(AFB1) were evaluated by using a three‐step medium‐term hepatocarcinogenesis assay. Diallyl sulfide (DAS) or diallyl disulfide (DADS) was added to the diet of rats (2 g/kg) for three weeks, during which NDEA or AFB1was administered by intraperitoneal injection. The rats were submitted later to eight days of 2‐acetylaminofluorene administration and to two‐thirds hepatectomy, then to phenobarbital administration. After eight weeks, liver preneoplastic foci expressing the placental form of glutathione S‐transferase were detected. The results show that DAS and DADS strongly reduced the number and the size of preneoplastic foci initiated by NDEA and AFB1, but especially by AFB1; DADS is more efficient than DAS. Most likely, the inhibition of the first step of hepatocarcinogenesis by allyl sulfides is related to the modulating effects that these compounds exert on the enzymes involved in activation and/or detoxication of the carcinogens. Our study demonstrated the chemopreventive potencies of dietary allyl sulfides in liver carcinogenesis induced by two potent hepatic carcinogens.

ISSN:0163-5581    

DOI:10.1080/01635589609514428

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractDiet‐induced changes in fecal excretion of secondary bile acids, certain neutral sterols, and bacterial enzyme activities are known to play a role in colon cancer development. Dietary fish oil (FO) has been implicated as a protective agent in colon carcinogenesis. In the present study, the effects of FO and corn oil (CO) on these fecal parameters were investigated in 24 healthy volunteers consuming a low‐or a high‐fat diet (30% or 50% of energy derived from fat). After four weeks of FO or CO supplementation (4.4 g of n‐3 fatty acids/day), no significant differences were noted for fecal activities ofβ‐glucuronidase,β‐glucosidase, and sulfatase, nor was fecal bile acid excretion significantly affected by FO or CO consumption. However, daily excretion of the putative colon carcinogen 4‐cholesten‐3‐one was significantly lower in the FO than in the CO period during low‐and high‐fat experiments. This may be another biochemical mechanism by which FO exerts its protective effect on colon cancer development.

ISSN:0163-5581    

DOI:10.1080/01635589609514429

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractExperimental dietary studies of human colorectal carcinogenesis are usually based on the AIN‐76A diet, which is dissimilar to human food in source, preparation, and content.The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet.The mean daily food intake composition of a previously evaluated adenoma patient case‐control study was used for the“human adenoma”(HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty‐four female Sprague‐Dawley rats were randomized and fed ad libitum the HA or the AIN‐76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined.Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation.This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

ISSN:0163-5581    

DOI:10.1080/01635589609514430

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

摘要:

AbstractThe present study assesses the potential of arecoline alkaloid to translactationally modify the chemopreventive efficacy of curcumin (diferuloyl methane) via neonatal modulation of hepatic biotransformation system enzymes. Curcumin (0.4 g/kg body wt/day) induced a significant increase in the hepatic levels of glutathione‐S‐transferase (GST), acid‐soluble sulfhydryl (SH), cytochrome b5, and cytochrome P‐450 in lactating dams and F1pups at 14 or 21 days. Arecoline (20 mg/kg body wt/day) could not modulate the hepatic GST and SH levels, although significant induction was observed in the levels of cytochrome b5and cytochrome P‐450 in dams and suckling pups. Significant enhancement of hepatic GST, SH, cytochrome b5, and cytochrome P‐450 levels was observed in groups treated with curcumin + arecoline. Curcumin‐induced levels of GST and SH were depressed whereas cytochrome b5and cytochrome P‐450 were further elevated by curcumin + arecoline treatment. The elevated levels of Phase I enzymes were more significant with exposure to curcumin + arecoline than with arecoline exposure alone. Modulation in competing potential pathways of biotransformation system enzymes in lactating dams may affect the rate and extent of maternal detoxication and thus influence the passage of metabolites of administered xenobiotics to the suckling neonate.

ISSN:0163-5581    

DOI:10.1080/01635589609514431

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor

ISSN:0163-5581    

DOI:10.1080/01635589609514422

出版商:Taylor&Francis Group    

年代:1996

数据来源: Taylor