Biomedical subjects

H L Newmark

Publications and source records attributed to H L Newmark.

At least 37 records · Page 2Linked to original sources

PubMed1997

Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells.

Treatment of human promyelocytic leukemia HL-60 cells with 10 muM curcumin for 48 h inhibited cellular proliferation and induced small increases in differentiation (100-200%) as measured by the proportion of cells that reduced nitroblue tetrazolium (NBT) and expressed Mac-1. Synergistic induction of differentiation as measured by the above markers was observed when 1-10 muM curcumin was combined with 10-100 nM all-trans retinoic acid (RA) or with 100 nM 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3). Cell morphology and flow cytometric studies (with the monocytic surface antigen CD14) indicated that combinations of RA and curcumin stimulated differentiation predominantly to granulocytes whereas combinations of vitamin D3 and curcumin stimulated differentiation predominantly to monocytes. Studies on cell cycle kinetics indicated that treatment of HL-60 cells with a combination of RA and curcumin for 48 or 96 h reduced the proportion of cells in the S phase of the cell cycle and increased the proportion of cells in the G0/G1 phase of the cell cycle to a greater extent than occurred for cells treated with either compound alone. Combinations of vitamin D3 and curcumin did not alter cell cycle kinetics to a greater extent than was observed for either compound alone. Combinations of RA and curcumin or vitamin D3 and curcumin inhibited the proliferation of HL-60 cells to a greater extent than was observed for either compound alone. The results indicate that curcumin is a weak stimulator of differentiation in HL-60 cells and that is has synergistic effects when combined with RA or vitamin D3. Combinations of curcumin and RA have a particularly potent inhibitory effect on the proliferation of HL-60 cells.

Antigens, Differentiation, Myelomonocytic↗

PubMed1997

Squalene, olive oil, and cancer risk: a review and hypothesis.

Epidemiological studies of breast and pancreatic cancer in several Mediterranean populations have demonstrated that increased dietary intake of olive oil is associated with a small decreased risk or no increased risk of cancer, despite a higher proportion of overall lipid intake. Experimental animal model studies of high dietary fat and cancer also indicate that olive oil has either no effect or a protective effect on the prevention of a variety of chemically induced tumors. As a working hypothesis, it is proposed that the high squalene content of olive oil, as compared to other human foods, is a major factor in the cancer risk-reducing effect of olive oil. Experiments in vitro and in animal models suggest a tumor-inhibiting role for squalene. A mechanism is proposed for the tumor-inhibitory activity of squalene based on its known strong inhibitory activity of beta-hydroxy-beta-methylglutaryl-CoA reductase catalytic activity in vivo, thus reducing farnesyl pyrophosphate availability for prenylation of the ras oncogene, which relocates this oncogene to cell membranes and is required for the signal-transducing function of ras.

Animals↗

PubMed1997

Inhibitory effects of curcumin on tumorigenesis in mice.

Curcumin (diferuloylmethane), the naturally occurring yellow pigment in turmeric and curry, is isolated from the rhizomes of the plant Curcuma longa Linn. Curcumin inhibits tumorigenesis during both initiation and promotion (post-initiation) periods in several experimental animal models. Topical application of curcumin inhibits benzo[a]pyrene (B[a]P)-mediated formation of DNA-B[a]P adducts in the epidermis. It also reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin inflammation, epidermal DNA synthesis, ornithine decarboxylase (ODC) mRNA level, ODC activity, hyperplasia, formation of c-Fos, and c-Jun proteins, hydrogen peroxide, and the oxidized DNA base 5-hydroxymethyl-2'-deoxyuridine (HmdU). Topical application of curcumin inhibits TPA-induced increases in the percent of epidermal cells in synthetic (S) phase of the cell cycle. Curcumin is a strong inhibitor of arachidonic acid-induced edema of mouse ears in vivo and epidermal cyclooxygenase and lipoxygenase activities in vitro. Commercial curcumin isolated from the rhizome of the plant Curcuma longa Linn contains 3 major curcuminoids (approximately 77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin). Commercial curcumin, pure curcumin, and demethoxycurcumin are about equipotent as inhibitors of TPA-induced tumor promotion in mouse skin, whereas bisdemethoxycurcumin is somewhat less active. Topical application of curcumin inhibits tumor initiation by B[a]P and tumor promotion by TPA in mouse skin. Dietary curcumin (commercial grade) inhibits B[a]P-induced forestomach carcinogenesis, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-induced duodenal carcinogenesis, and azoxymethane (AOM)-induced colon carcinogenesis. Dietary curcumin had little or no effect on 4-(methylnitosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis and 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in mice. Poor circulating bioavailability of curcumin may account for the lack of lung and breast carcinogenesis inhibition.

Administration, Oral↗

PubMed1996

Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis.

Inducible cyclooxygenase (Cox-2), also known as prostaglandin H synthase 2 (PGH-2) is a key enzyme in the formation of prostaglandins and thromboxanes. Cox-2 is the product of an immediate-early gene that is expressed in response to growth factors, tumor promoters, or cytokines. Overexpression of Cox-2 is associated with both human colon cancers and suppression of apoptosis in cultured epithelia] cells, an activity that is reversed by the nonsteroidal anti-inflammatory drug, sulindac sulfide. To address the relationship between Cox-2, apoptosis, and tumor development in vivo, we studied C57BL/6J-Min/+(Min) mice, a strain containing a fully penetrant dominant mutation in the Apc gene, leading to the development of gastrointestinal adenomas by 110 days of age. Min mice were fed AIN-76A chow diet and given sulindac (0.5 +/- 0.1 mg/day) in drinking water. Control Min mice and homozygous C57BL/6J-+/+ normal littermates lacking the Apc mutation (+/+) were fed AIN-76A diet and given tap water to drink. At 110 days of age, all mice were sacrificed, and their intestinal tracts were examined. Control Min mice had 11.9 +/- 7.8 tumors per mouse compared to 0.1 +/- 0.1 tumors for sulindac-treated Min mice. As expected, +/+ littermates had no macroscopic tumors. Examination of histologically normal-appearing small bowel from Min animals revealed increased amounts of Cox-2 and prostaglandin E(2) compared to +/+ littermates. Using two different in situ techniques, terminal transferase-mediated dUTP nick end labeling and a direct immunoperoxidase method, Min animals also demonstrated a 27-47% decrease in enterocyte apoptosis compared to +/+ animals. Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis. These data suggest that overexpression of Cox-2 is associated with tumorigenesis in the gastrointestinal epithelium, and that both are inhibited by sulindac administration.

Adenomatous Polyposis Coli↗

PubMed1996

Plant phenolics as potential cancer prevention agents.

The frequent consumption of fresh fruits and vegetables is associated with a lower cancer incidence in humans, and in experimental carcinogenesis. There are several groups of substances in plant foods which may contribute to this inhibition of tumor development. Almost all fresh fruits, vegetables and cereal grains contain appreciable amounts of naturally occurring plant phenolics. A brief overview will be presented of the most common plant phenolics in human foods and their chemical and biochemical properties. Plant phenolics, originally hypothesized to inhibit mutagenesis and/or carcinogenesis by virtue of antioxidant or electrophile trapping mechanisms, can also act as potent modulators of arachidonic metabolism cascade pathways. Certain plant phenols can be effective inhibitors of chemical mutagens, in vitro, and/or carcinogenesis in vivo. The historical origins, hypotheses of actions, current status and potential adverse effects of the utility of plant phenolics to reduce risk of cancer are discussed, as well as future possibilities and needs and objectives for future research.

Animals↗

PubMed1995

Butyrate and phenylacetate as differentiating agents: practical problems and opportunities.

Differentiating agents, including butyrate, phenylacetate and several other agents, have long been known to alter abnormal or transformed cell lines in vitro to a more normal state including phenotype and function. The effect depends on prolonged exposure to a minimum concentration of the agent. In vivo studies of butyrate and analogues have been limited, largely due to rapid in vivo metabolism. A butyrate prodrug, the triglyceride tributyrin, shows great promise in achieving effective and prolonged serum levels when given orally to mice and rats, and has been recommended for human trial. In vitro, butyrate and its mono- and triglyceride have shown potent synergy with retinoic acid, suggesting a ten-fold reduction in serum level requirements. Other butyrate prodrugs have been prepared and studied; several sugar esters of butyrate show promise. Phenylacetate, a normal mammalian metabolite, is also a potent differentiating agent, but its clinical use is limited by its objectionable odor per se and in treated subjects. Phenylbutyrate, a prodrug of phenylacetate, is more acceptable and may have greater promise. The availability of effective prodrugs of effective differentiating agents, such as tributyrin and phenylbutyrate, creates many opportunities for possible therapeutic and chemopreventive applications, especially if synergy in vivo can be demonstrated with retinoids (e.g., retinoic acid) or deltanoids (e.g., active vitamin D analogues), confirming in vitro studies. Particular disease targets would include certain leukemias, thalassemia, and sickle cell anemia.

Animals↗

PubMed1995

Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion.

Commercial grade curcumin (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemethoxycurcumin) is widely used as a yellow coloring agent and spice in foods. In the present study topical application of commercial grade curcumin, pure curcumin or demethoxycurcumin had an equally potent inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in ornithine decarboxylase activity and TPA-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Bisdemethoxycurcumin and tetrahydrocurcumin were less active. In additional studies we found that commercial grade curcumin, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin had about the same potent inhibitory effect on TPA-induced inflammation of mouse ears, as well as TPA-induced transformation of cultured JB6 (P+) cells. Tetrahydrocurcumin was less active. The results indicate that pure curcumin and demethoxycurcumin (the major constituents of commercial grade curcumin) have the same potent inhibitory effects as commercial grade curcumin for inhibition of TPA-induced tumor promotion, but bisdemethoxycurcumin and tetrahydrocurcumin are less active.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Inhibition of Western-diet induced hyperproliferation and hyperplasia in mouse colon by two sources of calcium.

A Western-style diet containing high-fat and phosphate, and low calcium and vitamin D was fed to mice for 20 weeks. Starting at week 8, subgroups of animals received the Western-style diet supplemented by two different calcium sources: tricalcium phosphate and calcium citrate malate. Hyperproliferation (increased [3H]thymidine-labelled cells/colonic crypt) and hyperplasia (increased total epithelial cells/crypt) developed in the sigmoid colon after 8 weeks of feeding the Western-style diet confirming previous results, and these were reversed at later periods by the addition of the two calcium sources to the Western-style diet. Findings indicate that the modified colonic epithelial cell hyperproliferation and hyperplasia which have been associated with subsequent development of colonic neoplasia, are induced in mice fed a Western-style diet, and the addition of calcium to the diet inhibited their development in the colonic mucosa.

Animals↗

PubMed1994

Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice.

Curcumin (diferuloylmethane), a yellow pigment that is obtained from the rhizomes of Curcuma longa Linn., is a major component of turmeric and is commonly used as a spice and food-coloring agent. The inhibitory effects of feeding commercial grade curcumin (77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin) in AIN 76A diet on carcinogen-induced tumorigenesis in the forestomach, duodenum, and colon of mice were evaluated. Administration p.o. of commercial grade curcumin in the diet inhibited benzo(a)pyrene-induced forestomach tumorigenesis in A/J mice, N-ethyl-N'-nitro-N-nitrosoguanidine-induced duodenal tumorigenesis in C57BL/6 mice, and azoxymethane (AOM)-induced colon tumorigenesis in CF-1 mice. Dietary commercial grade curcumin was given to mice at: (a) 2 weeks before, during, and for 1 week after carcinogen administration (during the initiation period); (b) 1 week after carcinogen treatment until the end of the experiment (during the postinitiation period); or (c) during both the initiation and postinitiation periods. Feeding 0.5-2.0% commercial grade curcumin in the diet decreased the number of benzo(a)pyrene-induced forestomach tumors per mouse by 51-53% when administered during the initiation period and 47-67% when administered during the postinitiation period. Feeding 0.5-2.0% commercial grade curcumin in the diet decreased the number of N-ethyl-N'-nitro-N-nitrosoguanidine-induced duodenal tumors per mouse by 47-77% when administered during the postinitiation period. Administration of 0.5-4.0% commercial grade curcumin in the diet both during the initiation and postinitation periods decreased the number of AOM-induced colon tumors per mouse by 51-62%. Administration of 2% commercial grade curcumin in the diet inhibited the number of AOM-induced colon tumors per mouse by 66% when fed during the initiation period and 25% when fed during the postinitiation period. The ability of commercial grade curcumin to inhibit AOM-induced colon tumorigenesis is comparable to that of pure curcumin (purity greater than 98%). Administration of pure or commercial grade curcumin in the diet to AOM-treated mice resulted in development of colon tumors which were generally smaller in number and size as compared to the control group of AOM-treated mice. These results indicate that not only did curcumin inhibit the number of tumors per mouse and the percentage of mice with tumors but it also reduced tumor size. Histopathological examination of the tumors showed that dietary curcumin inhibited the number of papillomas and squamous cell carcinomas of the forestomach as well as the number of adenomas and adenocarcinomas of the duodenum and colon.

Adenocarcinoma↗

PubMed1994

Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated SKH-1 mice.

In a previous study (Z. Y. Wang et al., Cancer Res., 52: 1162-1170, 1992), we found that administration of a water extract of green tea leaves as the sole source of drinking fluid inhibited ultraviolet B light (UVB)-induced carcinogenesis in SKH-1 mice previously initiated with 7,12-dimethylbenz[a]anthracene (DMBA). In the present study, we compared the effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on UVB-induced skin carcinogenesis in DMBA-initiated SKH-1 mice. A 1.25% water extract of each kind of tea leaf (1.25 g tea leaf/100 ml water) was prepared by passing 4 liters of hot water through 50 g of tea leaves in a Bunn tea brewing machine. The mean concentrations of solids in multiple samples of 1.25% black tea, green tea, decaffeinated black tea, and decaffeinated green tea analyzed during the course of this study were 4.23, 3.94, 3.66, and 3.53 mg/ml, respectively. These concentrations of tea solids are similar to those present in tea brews ingested by humans. Female SKH-1 mice were treated topically with 200 nmol of DMBA, followed 3 weeks later by irradiation with 30 mJ/cm2 of UVB twice weekly for 31 weeks. UVB-induced formation of skin tumors was markedly inhibited by oral administration of 0.63 or 1.25% black tea, green tea, decaffeinated black tea, or decaffeinated green tea as the sole source of drinking fluid 2 weeks prior to and during 31 weeks of UVB treatment. Administration of each of the eight tea preparations not only inhibited the number of tumors, but tumor size was also markedly decreased. Histopathological examination of each tumor showed that oral administration of the eight tea preparations had a marked inhibitory effect on the formation of UVB-induced keratoacanthomas and carcinomas. Administration of 1.25% black tea, green tea, decaffeinated black tea, or decaffeinated green tea inhibited the number of keratoacanthomas per mouse by 79, 78, 73, or 70%, respectively, and the number of carcinomas per mouse was inhibited by 93, 88, 77, or 72%, respectively. In summary, administration of black tea was comparable to green tea as an inhibitor of UVB-induced skin carcinogenesis in DMBA-initiated SKH-1 mice. Oral administration of decaffeinated black tea or decaffeinated green tea also had a marked inhibitory effect on UVB-induced skin carcinogenesis in DMBA-initiated SKH-1 mice, but these tea preparations were slightly less effective than the regular teas at the high dose level.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Butyrate as a differentiating agent: pharmacokinetics, analogues and current status.

The field of butyrate-induced differentiation of neoplastic and non-neoplastic cells is reviewed and possible clinical correlations considered with regard to butyrate, butyrate prodrugs and butyrate analogues. These topics are discussed from the point of view of the concentrations required in vitro for biologic effect, and likely pharmacokinetic behavior in vivo.

Anemia, Sickle Cell↗

PubMed1994

Vitamin D adequacy: a possible relationship to breast cancer.

(1) Low levels of dietary calcium and vitamin D, biochemically interrelated, increase the promoting action of high dietary fat on chemically induced mammary carcinogenesis in animal studies. (2) High dietary fat increases mammary epithelial cell proliferation, particularly the "hormonally driven" hyperproliferation during breast growth and development in young animals. Increased dietary calcium (and probably vitamin D) lessens the increase of proliferation induced by high fat. These data, although limited, suggest that the maximum effect of diet (high fat increase, as well as calcium and vitamin D modulation) on eventual breast cancer may be during puberty, and adolescence, when the mammary gland is actively growing and developing. (3) An inverse epidemiological correlation has been developed between sunlight availability as a source of vitamin D and the risk of breast cancer in the U.S. and Canada. (4) Current vitamin D and calcium dietary intake in the U.S. is far below the RDA in all female age groups, particularly for the elderly. (5) Reduction of breast cancer risk, and simultaneously osteoporosis, might be achieved by increasing dietary intake of calcium and vitamin D to RDA levels. This may be particularly applicable to females during puberty and adolescence.

Animals↗

PubMed1994

Effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate- and ultraviolet B light-induced expression of c-Jun and c-Fos in JB6 cells and in mouse epidermis.

Expression of c-jun protein (c-Jun) was observed in normally proliferating JB6 cells but not in confluent cells. Reduction of the serum concentration from 5% to 2% in the cell culture medium caused JB6 cells to enter a quiescent non-proliferating state and down-regulated the expression of c-Jun. Treatment of quiescent JB6 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 ng/ml) for 24 h markedly stimulated the formation of c-Jun and caused morphological changes. Treatment of JB6 cells with TPA for 48 h resulted in transformed foci with mixed cell populations. Although some cells in these foci expressed high levels of c-Jun, many other cells did not. The increased expression of c-Jun and morphological changes observed at 24 h after treatment of JB6 cells with TPA (10 ng/ml) was inhibited by curcumin (10 nmol/ml). Treatment of JB6 cells with 2.5, 5 or 10 nmol curcumin/ml inhibited the formation of TPA-induced anchorage-independent colonies that grow in soft agar by 31%, 43% and 77%, respectively. Although inhibition of cell proliferation was not observed with 2.5 nmol curcumin/ml, higher concentrations did inhibit cell proliferation. Topical application of 5 nmol TPA to the backs of CD-1 mice once a day for 5 days caused epidermal hyperplasia and the levels of c-Jun were increased in the suprabasal layer of the epidermis and in the muscle layer of the dermis. This treatment also increased c-fos protein (c-Fos) expression in the muscle layer, but there was little or no increase in the expression of c-Fos in the basal or suprabasal layer of the epidermis. Topical application of 10 mumol curcumin together with 5 nmol TPA once a day for 5 days strongly inhibited TPA-induced epidermal hyperplasia and c-Jun and c-Fos expression. A single application of 180 mJ/cm2 of ultraviolet B light (UVB) to the backs of SKH-1 mice caused epidermal hyperplasia and expression of c-Fos and c-Jun in the muscle layer of the dermis and of c-Fos in the suprabasal layer of the epidermis. Maximum effects were observed at 6 days after UVB exposure. Application of 10 mumol curcumin to mouse skin twice a day for 5 days immediately after UVB exposure had only a small/variable inhibitory effect on UVB-induced increases in the expression of c-Fos and c-Jun and on epidermal hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

The effect of dietary quercetin and rutin on AOM-induced acute colonic epithelial abnormalities in mice fed a high-fat diet.

Dietary quercetin (QU) and rutin (RU), phenolic flavonoids found in many fruits and vegetables, when fed to mice on a low-fat diet successfully modified the response to azoxymethanol (AOM) by initially inhibiting hyperproliferation and the formation of foci of dysplasia (FADs) and ultimately reducing tumor incidence (Carcinogenesis 12, 1193-1196, 1991). In this study, we tested the efficacy of QU and RU when a high-fat diet was presented. An AIN 76A diet made with 20% corn oil (CO) was supplemented with QU (0.5%, 2.0%, or 5.0%) and RU (2.0% or 4.0%). These five diets, as well as a 5.0% and a 20.0% CO diet, were fed to a group of CF1 female mice for nine weeks. Both QU and RU showed nonsignificant dose-related trends toward normalization of the AOM-induced upward extension of S phase cells. Examination of 500 microns of serially sectioned distal colon revealed that 29% of mice fed the 20% CO control diet were free of FADs. Among the mice fed QU, regardless of dose, > 80% were free of FADs. When the three groups fed QU were pooled and compared with the control 20% CO-fed mice, the degree of protection was significant (p < 0.01). Mice fed RU expressed a level of protection that bordered on the significant (p < 0.08). These data suggest that, regardless of the fat content of the diet, QU and RU are capable of modifying or inhibiting events in the development of chemically induced colonic neoplasia.

Animals↗

PubMed1992

Modulation of colonic epithelial cell proliferation, histone acetylation, and luminal short chain fatty acids by variation of dietary fiber (wheat bran) in rats.

The effect of increasing amounts of wheat bran (0, 5, 10, 20%) in AIN-76 semisynthetic diet on colonic luminal short chain fatty acids, epithelial cell histone acetylation, and cytokinetics, was studied for 2 weeks in groups of 10 male Sprague-Dawley rats. Luminal contents were removed from the colon at sacrifice, quick frozen, and analyzed for short chain fatty acids by gas-liquid chromatography. Histone acetylation was assessed in cells isolated from the same animals. Cell proliferation was measured after a short pulse in vivo with [3H]thymidine. Colonic luminal butyrate levels were lower in the 0 and 20% fiber groups, and higher in the 5 and 10% fiber groups. In contrast, cell proliferation, as determined by labeling index, was higher in the 0 and 20% fiber groups, and lower in the 5 and 10% fiber groups. This resulted in a significant inverse correlation between luminal butyrate levels and colonic cell proliferation. In addition, there was a positive linear correlation between luminal butyric acid levels and colon epithelial cell histone acetylation. From these data it was concluded that colonic butyrate levels can be modulated by the addition of wheat bran to the diet and that butyrate can modulate DNA synthesis (calculated as labeling index) in the proliferative compartments of colonic crypts. The localization of dividing cells was unchanged and no induction of terminal differentiation was detectable (contrary to what has been observed for transformed cells in culture).

Acetylation↗

PubMed1992

Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced colonic epithelial cell proliferation and focal areas of dysplasia.

Curcumin, a major yellow pigment of turmeric obtained from powdered rhizomes of the plant Curcuma longa Linn., is commonly used as a coloring agent in foods, drugs and cosmetics. Ascorbyl palmitate is a lipid soluble derivative of ascorbic acid. Both curcumin and ascorbyl palmitate have antioxidant activity and are potent inhibitors of 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin. The effects of dietary curcumin and ascorbyl palmitate on azoxymethanol (AOM)-induced hyperproliferation of colonic epithelial cells and the incidence of focal areas of dysplasia (FADs) were evaluated in female CF-1 mice fed an AIN 76A diet. Subcutaneous injections of AOM (10 mg/kg body wt. once weekly for 6 weeks) caused hyperplasia and the formation of FADs in the colon. Administration of 2% curcumin in the diet inhibited AOM-induced formation of FADs while administration of 2% ascorbyl palmitate in the diet did not demonstrate inhibition. This result suggests that dietary curcumin may inhibit AOM-induced colonic neoplasia in mice.

Animals↗

PubMed1992

Calcium, vitamin D, and colon cancer.

Calcium contributes to the progression of epithelial cells through all phases of the proliferative cycle and into stages of cell differentiation; intracellular concentrations of calcium that are required for cell renewal, however, are lower than those required for epithelial-cell differentiation. These effects of calcium are modulated by interactions with 1,25-dihydroxy-vitamin D3, phosphate, and fatty acids, all of which are partly dependent on dietary intake. In rodent models, increased dietary calcium inhibited hyperproliferation of colon epithelial cells induced by increased levels of fatty acids or bile acids present in the colon. When carcinogens induced hyperproliferation of colon epithelial cells the hyperproliferation was decreased by added dietary calcium, and in several animal models the occurrence of carcinogen-induced carcinomas of the colon decreased with increased dietary calcium. A nutritional stress diet, designed to represent human Western dietary intake of calcium, phosphate, vitamin D, and fat, produced hyperproliferation and hyperplasia in the colons of rodents; these effects were reduced by increasing dietary levels of calcium. Decreased levels of ornithine decarboxylase also were reported in human and rodent colon mucosa exposed to increasing levels of calcium. In human subjects at increased risk for familial colon cancer, hyperproliferation of colon epithelial cells was reduced after oral dietary supplementation with calcium. In epidemiological studies, several investigators reported inverse correlations between levels of dietary calcium intake and the incidence of colon cancer. Extrapolation of the data have suggested a protective effect of total calcium intakes above 1500 to 1800 mg/day.

1,2-Dimethylhydrazine↗

PubMed1992

Stability of a commercially prepared fish oil (omega-3 fatty acid) laboratory rodent diet.

There is evidence that highly unsaturated omega-3 fatty acids present in fish oils can provide a cancer-protective effect; however, when added to laboratory rodent formulations, these fatty acids are subject to rapid and/or extensive oxidation and other chemical changes by exposure to air, light, or heat during processing of pellets or when stored for various lengths of time. An animal diet with 16% refined fish oil and 4% corn oil was commercially prepared with antioxidants (butylated hydroxytoluene and butylated hydroxyquinone in addition to alpha-tocopherol) present, and precautions were taken to prevent oxidation at all stages of production and handling. Fatty acid composition of dried powdered diet as well as freshly processed dried pellets was analyzed from four lots at the beginning and end of a 45-day feeding period. Additionally, fatty acid analyses were carried out on pellets dried by both vacuum and air techniques, and pellets were left exposed to air at room temperature for 96 hours. No statistical difference in overall fatty acid composition was observed among lots due to pelletization or drying procedures. Moreover, 4 days of exposure of pellets to air at ambient temperatures and 45 days of freezer storage had no significant effect on their fatty acid composition. It would appear that rodent diets containing omega-3 fatty acids can be reliably prepared commercially and safely substituted for diets prepared manually and in bulk on a weekly basis.

Animal Feed↗