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C Ip

Publications and source records attributed to C Ip.

At least 73 records · Page 4Linked to original sources
PubMed1994

Comparison of the effects of an organic and an inorganic form of selenium on a mammary carcinoma cell line.

The development of new compounds with greater cancer inhibitory activity and that are well tolerated continues to be a priority in chemoprevention research involving selenium. One compound, 1,-4-phenylene-bis(methylene)selenocyanate (p-XSC), is representative of a series of organoselenium compounds with these characteristics. In this study, the effects of p-XSC on a mouse mammary carcinoma cell line were compared to those of sodium selenite, which has been shown to be growth inhibitory. Treatment with p-XSC caused a 3- to 6-fold greater accumulation of selenium within cells than did treatment with equivalent amounts of selenite and cells were able to better tolerate higher cellular levels of selenium derived from p-XSC. Both compounds resulted in a dose-dependent reduction in cell number after 24 h of exposure. Selenite and p-XSC also caused a dose-dependent increase in cell death by apoptosis. This effect was observed within 5 h of treatment. The effect of p-XSC on apoptosis was more pronounced than that of selenite, especially at the 20 microM level of exposure. The induction of apoptosis by selenium compounds may partially account for their chemopreventive activity.

Animals↗
PubMed1994

Comparative effect of inorganic and organic selenocyanate derivatives in mammary cancer chemoprevention.

Recently El-Bayoumy and coworkers have reported that 1,4-phenylene-bis(methylene)selenocyanate (p-XSC) was very effective in inhibiting 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis and adduct formation during the initiation phase (Cancer Res., 52, 2402-2407, 1992). Furthermore, this compound was found to be well tolerated by rats at high doses. The present study was designed to extend these earlier observations by investigating the response to lower levels of p-XSC given either before or after DMBA administration. At a level of 15 p.p.m. Se, p-XSC suppressed total mammary tumor yield by 80% and 52% in the initiation phase and post-initiation phase, respectively. A dose-response effect was evident in the range 5-15 p.p.m. Se. When p-XSC was given at a level of 5 p.p.m. Se during the entire course of the experimental period, total tumor yield was reduced by half. This dose is about 4 x less than the maximum tolerable dose (MTD). Other selenocyanate analogs were also examined in an attempt to obtain information on their respective chemopreventive index, which is calculated as the ratio of MTD to the effective dose which produces approximately a 50% inhibition in total tumor yield (ED50). The reagents studied included potassium selenocyanate, methyl selenocyanate and benzyl selenocyanate, as well as sodium selenite (reference compound). Compared to p-XSC, which has a chemopreventive index of 4.0, the other four compounds have a lower index ranging from 1.3 for sodium selenite and potassium selenocyanate to 2.0 for methyl selenocyanate and 2.5 for benzyl selenocyanate. A high chemopreventive index signifies that a compound is well tolerated at doses required for cancer suppression. The last component of the present study involved the repletion assay of liver glutathione peroxidase in selenium-deficient rats as a biomarker to estimate the metabolizability of the above selenium compounds. The bioavailability data suggest that the selenium from p-XSC is not as efficiently incorporated into glutathione peroxidase as the selenium from selenite or the other selenocyanate analogs. Currently, we are working under the hypothesis that the chemical structure of the RSeCN compound could affect activity per se and also influence the rate of release of selenium from the parent compound, thereby impacting on the anticarcinogenic efficacy, tolerance and bioavailability of the compound.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Characterization of tissue selenium profiles and anticarcinogenic responses in rats fed natural sources of selenium-rich products.

The present report describes the biological effects associated with the feeding of three selenium-rich natural products in rats: high-selenium garlic, high-selenium onion and Brazil nut. The first two are experimental crops cultivated with selenium fertilization. Brazil nut is probably the only unadulterated high-selenium food that is available commercially. Tissue selenium profiles, liver glutathione concentrations and mammary cancer inhibition (in the dimethylbenz[a] anthracene model) were the endpoints of investigation. Parallel designs were set up to compare the three high-selenium products with selenite and selenomethionine. Previous studies have shown that treatment with seleno-methionine resulted in significantly greater tissue selenium accumulation, particularly in skeletal muscle, than treatment with selenite. In contrast, selenite, but not selenomethionine, induced a modest increase in liver glutathione concentrations. The objective was to determine whether the high-selenium natural products elicited responses that were similar to that of selenite or selenomethionine. Our experiments suggested that the high-selenium garlic and onion might have some unique attributes. First, their ingestion did not lead to an exaggerated accumulation of tissue selenium, a concern that was shared by both selenomethionine and Brazil nut. Second, unlike selenite, they did not cause any perturbation in glutathione homeostasis. Third, they expressed good anticancer activity that was equal to, if not better than, that of selenite. The chemical form(s) of selenium present in the high-selenium Allium vegetables will be discussed in relation to the manifestation of the above characteristics.

Allium↗
PubMed1994

Enrichment of selenium in allium vegetables for cancer prevention.

We previously reported that garlic cultivated with selenium fertilization is superior to regular garlic in mammary cancer prevention in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model (Nutr. Cancer, 17, 279-286, 1992). A new crop of high-selenium garlic was harvested in 1992 and was used in a dose-response study to confirm the reproducibility of the product and the bioassay. Supplementation of 1 or 2 p.p.m. Se in the diet from the high-selenium garlic produced a 56% or 75% reduction respectively in the total tumor yield. Since both garlic and onion belong to the same allium family of vegetables, we were also interested in finding out whether our experience with garlic could be similarly applied to onion. A high-selenium onion crop was grown in the same season and location and with the same schedule of selenium fertilization. Two distinct differences were noted with the high-selenium onion regarding its capacity to accumulate selenium and its efficacy in cancer prevention. First, the selenium concentration in onion was considerably lower (28 p.p.m. Se dry wt) as compared to that found in garlic (110-150 p.p.m. Se). Second, given the same levels of selenium supplementation, the high-selenium onion was apparently not as powerful as the high-selenium garlic in mammary cancer inhibition. Thus different plants, even those of the same genus, may respond in their unique way to selenium fertilization and the biological benefits of selenium enrichment may vary depending on the species. Additional information from our study indicated that the high-selenium garlic/onion might provide an ideal system for delivering selenium-substituted analogs in a food form for cancer prevention: (i) they expressed a good range of anticancer activity and could be easily adapted for human consumption on a regular basis; (ii) their ingestion did not result in an excessive accumulation of tissue selenium, a concern that is associated with the standard selenium compounds such as selenite and selenomethionine; (iii) no perturbation in the maintenance of functional selenoenzymes were observed even at high levels of supplementation.

Allium↗
PubMed1993

Controversial issues of dietary fat and experimental mammary carcinogenesis.

Epidemiological evidence from different countries worldwide has suggested a positive association between the availability of fat in the diet and variations in breast cancer mortality rate. A voluminous amount of information is also available in the literature linking increased fat consumption, particularly polyunsaturated fat, and stimulation of mammary tumorigenesis in animal models. In the past few years, our laboratory has been studying the impact of several confounding factors that could modulate the enhancing effect of fat on neoplastic development of the mammary gland in female rats which are treated with a carcinogen. It is our conclusion that fat promotes mammary carcinogenesis only under a very stringent set of conditions which might not be duplicated in the arena of fat intake and human breast cancer risk. Previous studies on fat and mammary cancer in experimental models have used young virgin rats which are given a dose of carcinogen at a particular age. The question arises as to whether the promoting effect of fat might be a consequence of the characteristics of the model. We have supportive evidence showing that the following criteria must be satisfied in order for fat enhancement of mammary carcinogenesis to be manifested: (a) carcinogen administered at a time when the mammary gland is exquisitely susceptible to tumor induction, (b) animals maintained on a semipurified diet, (c) ad libitum feeding necessary, and (d) unusually high requirement of linoleic acid for tumor development. On the other hand, the stimulatory effect of fat is attenuated or sometimes even negated by (a) feeding of a natural ingredient diet, (b) submaximal calorie intake, and (c) previous history of pregnancy and lactation. Given the spectrum of confounders that are inherent in epidemiological studies linking fat intake and breast cancer, including differences in lifestyle, reproductive history, eating habits, as well as complexity of the total diet, our findings suggest that there may be a need to reevaluate the validity of extrapolating animal data that are obtained under a highly defined set of conditions to the etiological significance of dietary fat in human breast cancer.

Animals↗
PubMed1993

Bioavailability of selenium from selenium-enriched garlic.

We previously reported that garlic grown in a selenium-fertilized medium (selenium-enriched garlic) is superior to regular garlic in mammary cancer prevention in an animal model (Nutr Cancer 17, 279-286, 1992). The present study was designed to evaluate the nutritional bioavailability of selenium from this garlic with use of two liver selenoenzymes as biomarkers: glutathione peroxidase and type I 5'-deiodinase. Rats were fed a selenium-deficient diet (0.01 ppm Se) from weaning for four weeks to deplete both enzymes. They were then supplemented with nutritional levels of selenium (0.1-0.5 ppm) in the form of sodium selenite (positive control) or selenium-enriched garlic. Our results showed that selenium-enriched garlic was just as effective as selenite in restoring the activity of both selenoenzymes. This was demonstrated in a time course repletion experiment as well as in a dose-response experiment. Thus the selenium in selenium-enriched garlic has potent nutritional and anticancer efficacy. The type I 5'-deiodinase enzyme catalyzes the conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and is responsible for most of the circulating T3. Because cancer chemoprevention by selenium usually requires pharmacological levels of selenium, we also examined the possible modulation of type I 5'-deiodinase by long-term feeding of selenium-enriched garlic at 3 ppm Se in the diet. The observation that a high intake of selenium-enriched garlic did not affect 5'-deiodinase activity suggests that its anticarcinogenic effect is unlikely to be mediated by an imbalance in the blood T4-to-T3 ratio.

Animals↗
PubMed1993

Metabolites of sodium selenite and methylated selenium compounds administered at cancer chemoprevention levels in the rat.

1. The metabolism of orally-administered sodium selenite and five methylated selenium compounds was investigated in the female rat at dosages equivalent to those used in other studies for prevention of mammary cancer. Dimethyl selenide (DMSe) exhaled within 24 h following dosing was measured, along with inorganic and monomethylated (MMSe) forms of selenium plus trimethylselenonium ion (TMSe+) in urine. 2. MMSe was the dominant metabolite of selenite given at low levels (0.1 ppm in the diet), but excretion of DMSe and TMSe+ increased sharply when selenite dosage was increased to the chemopreventive range of 3 ppm dietary Se. When similar chemopreventive levels of mono-, di-, or trimethylated compounds were administered, the total quantity of methylated metabolites was greater than for selenite and the metabolite profile reflected the expected point of entry into the intermediary metabolism pathway; the major metabolites were MMSe from Se-methylselenocysteine, DMSe from selenobetaine methyl ester, and TMSe+ from selenobetaine. However, the profile of metabolites provided clear evidence that the methylated selenium compounds underwent demethylation, as shown by the excretion of inorganic and MMSe. Selenium administered as dimethyl selenoxide was almost completely excreted and about 90% of the dose was recovered as DMSe, indicating that reduction was the major pathway. For TMSe+, about 10% of the dose was excreted as DMSe and 84% as TMSe+. 3. A low, non-toxic level of sodium arsenite (5 ppm As in the diet) that is known to modify differentially the anticarcinogenic activity of selenite and methylated selenium compounds did not modify the excretion of the methylated selenium metabolites. 4. It is concluded that high anticarcinogenic activity is associated with extensive excretion of methylated Se excretory metabolites, but high output of such metabolites per se does not necessarily lead to anticarcinogenic activity. The whole animal has extensive capabilities for interconverting forms of selenium, and retains significant amounts in tissues, complicating the interpretation of Se metabolism and anticarcinogenic action. Further research is needed on the forms of selenium present in tissues.

Animals↗
PubMed1992

Biological activities of trimethylselenonium as influenced by arsenite.

The present study was designed to evaluate three biological activities of trimethylselenonium (TMSe+): anticarcinogenicity, toxicity, and nutritional availability. These experiments were carried out in female rats both in the presence and absence of arsenite because arsenite is known to affect selenium metabolism. Supplementation with TMSe+ by itself in the diet, at levels of 20, 40, or 80 ppm Se, did not offer any protection against mammary carcinogenesis induced by dimethylbenz(a)anthracene. On the other hand, the coadministration of arsenite (5 ppm As) with the two higher levels of TMSe+ resulted in significant tumor suppression. In the acute toxicity experiment, rats were injected subcutaneously with 0.5 or 1 mg Se/kg, preceded 15 minutes earlier by arsenite at doses of 0.5, 1, or 2 mg As/kg. Although treatment with TMSe+ or arsenite alone did not produce any sign of toxicity, a synergistic toxic effect was evident with the combination. Regarding the ability of TMSe+ to restore hepatic glutathione peroxidase following selenium depletion, it was found that a dietary level of 40 ppm Se was necessary for complete recovery. The nutritional biopotency of TMSe+ was not sensitive to either up- or down-regulation by arsenite under conditions where arsenite also enhanced the anticarcinogenic activity of TMSe+. The contrasting effects of arsenite on these two end points suggest that different forms of selenium are involved. It is hypothesized that arsenite might increase the production of a critical metabolite from methylated selenides. However, there is no clear evidence at the present time to suggest whether the same intermediate(s) is responsible for both anticarcinogenicity and toxicity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Mammary cancer prevention by regular garlic and selenium-enriched garlic.

The anticarcinogenic activities of regular (soil-grown) garlic and selenium-enriched garlic (cultivated in the greenhouse) were evaluated using the 7,12-dimethylbenz[a]anthracene-(DMBA) induced mammary tumor model in rats. In Experiment 1, milled regular garlic powder was added to the basal AIN-76A diet at 20 g/kg. The results from different schedules of supplementation suggested that a continuous treatment, which started before DMBA and persisted for the entire duration of the study, was most effective in tumor suppression. In Experiment 2, selected allyl group-containing sulfides that are normal constituents of garlic extract were given by gavage in three single doses immediately before DMBA. Several structurally related compounds were found to be protective during the initiation phase in the mammary cancer model. Although the present study was not designed specifically to elucidate the structure-activity relationship with respect to sulfur chain length or alkyl versus alkenyl substitution, our data showed that diallyl disulfide was more active than diallyl sulfide or allyl methyl sulfide. In Experiment 3, the anticarcinogenic activity of selenium-enriched garlic (containing 150 ppm Se dry weight from growth in a selenium-fertilized medium) was compared with that of regular garlic as well as selenite. Animals given the selenium-enriched garlic (final concentration 3 ppm Se in the diet) developed the fewest mammary tumors. Tissue selenium levels, however, were lower in these animals than in those fed the same amount of selenium from selenite. Our study demonstrated the feasibility of achieving cancer prevention with the use of a selenium-rich food system.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Comparison of selenium and sulfur analogs in cancer prevention.

Several organoselenium compounds have been shown to have powerful anticarcinogenic activity. In view of certain similarities between selenium and sulfur biochemistry, we have evaluated the chemopreventive efficacy of three pairs of analogs using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats. The compounds tested were selenocystamine/cysteamine, Semethylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine. In the first study, each agent was added to the basal AIN-76A diet and was given before and continued after DMBA treatment until the end. All three selenium compounds were active; a 50% inhibition was achieved at approximately 25 x 10(-6) mol/kg with Se-methylselenocysteine and selenobetaine and at approximately 40 x 10(-6) mol/kg with selenocystamine. In the sulfur series, only cysteamine and S-methylcysteine produced anticancer activity, and the levels required for comparable responses were 500- to 750-fold higher compared to the corresponding selenium analogs. Sulfobetaine was inactive even when present at near maximally tolerated levels. In the second study, Se-methylselenocysteine and S-methylcysteine were chosen for further examination during the initiation and post-initiation phases of mammary carcinogenesis. Se-Methylselenocysteine was effective when it was given either before or after DMBA administration. In contrast, S-methylcysteine was effective only after DMBA treatment. Thus, compared to the sulfur structural analogs, selenium compounds are much more active in cancer protection and may have a multi-modal mechanism in preventing cellular transformation as well as in delaying or inhibiting the expression of malignancy after carcinogen exposure.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.

In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants.

Animals↗
PubMed1991

Mammary cancer prevention by conjugated dienoic derivative of linoleic acid.

Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose-dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Chemical form of selenium, critical metabolites, and cancer prevention.

Methylated selenides are prominent metabolites at the dietary levels used for obtaining anticarcinogenic effects with selenium. The present study reports the chemopreventive activities of 2 novel selenium compounds, Se-methylselenocysteine and dimethyl selenoxide, in the rat dimethylbenz(a)anthracene-induced mammary tumor model. Other treatment groups were supplemented with either selenite or selenocystine for comparative purposes. Each selenium compound was tested at different levels and was given to the animal starting 1 week before dimethylbenz(a)anthracene administration and continued until sacrifice. Results of the carcinogenesis experiments showed that the relative efficacy with the four compounds was Se-methylselenocysteine greater than selenite greater than selenocystine greater than dimethyl selenoxide. In correlating the chemical form and metabolism of these selenium compounds with their anticarcinogenic activity, it is concluded that: (a) selenium compounds that are able to generate a steady stream of methylated metabolites, particularly the monomethylated species, are likely to have good chemopreventive potential; (b) anticarcinogenic activity is lower for selenoamino acids, such as selenocysteine following conversion from selenocystine, which have an escape mechanism via random, nonstoichiometric incorporation into proteins; and (c) forms of selenium, as exemplified by dimethyl selenoxide, which are metabolized rapidly and quantitatively to dimethyl selenide and trimethylselenonium and excreted, are likely to be poor choices. We also undertook a separate bioavailability study using Se-methylselenocysteine, dimethyl selenoxide, and trimethylselenonium as the starting compounds for delivering selenium with one, two, or three methyl groups, and measured the ability of these compounds to restore glutathione peroxidase activity in selenium-depleted animals. All three compounds were able to fully replete this enzyme, although with a wide range of efficiency (Se-methylselenocysteine greater than dimethyl selenoxide greater than trimethylselenonium), suggesting that complete demethylation to inorganic selenium is a normal process of selenium metabolism. However, the degree to which this occurs under chemoprevention conditions would argue against the involvement of selenoproteins in the anticarcinogenic action of these selenium compounds.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Changes in ornithine decarboxylase activity and polyamine levels in response to eight different forms of selenium.

The biological activity of selenium is known to depend on its chemical form. In this study, eight forms of selenium that differed in oxidation state or degree of methylation were studied for their acute effects on the activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMet DC) and on the concentrations of the polyamines putrescine, spermidine, and spermine in the liver. The polyamine pathway was studied because it is involved in the control of cell growth and in the cell's response to trophic, carcinogenic, and toxic stimuli, activities that selenium has been reported to affect. Female Sprague Dawley rats were administered 12 mumol Se/kg body weight via intraperitoneal injection and were sacrificed six hours later. Injection of sodium selenate, sodium selenite, selenomethionine, Se-methylselenocysteine, selenobetaine, and selenobetaine methyl ester resulted in significant increases in liver selenium, whereas injection of dimethylselenoxide and trimethylselenonium chloride did not. ODC activity and AdoMet DC activity were induced by those selenium compounds that also increased liver selenium content, but the magnitude of enzyme induction by those compounds was not correlated with the hepatic concentration of total selenium determined fluorometrically. Furthermore, the induction of ODC activity by the various forms of selenium did not result in concomitant increases in putrescine, spermidine, and spermine except in the case of selenite. Given that alterations in the metabolism of selenium are induced when the level of tissue selenium is elevated and that the relative abundance of various selenometabolites can be affected by the point of entry of selenium into intermediary metabolism, these data suggest that the changes that were observed in enzyme activities and polyamine levels are likely to be associated with the accumulation of a specific metabolite of selenium. The relevance of these findings to elucidation of the biological activities attributable to various forms of selenium is under investigation.

Adenosylmethionine Decarboxylase↗
PubMed1991

Combination of blocking agents and suppressing agents in cancer prevention.

The design of the present study was based on the premise that if blocking agents and suppressing agents are targeted at different phases of chemical carcinogenesis, a greater chemopreventive effect would be achieved by using the combination treatment compared to the single-agent treatment. The dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats was used to test this hypothesis, with the blocking agent given before DMBA only and the blocking agent given after DMBA until the end of the experiment. A total of three sets of combination treatment were carried out; diallyl sulfide/Se-methylselenocysteine, ellagic acid/selenomethionine, and diallyl sulfide/quercetin. In all three cases, the combination regimen was much more effective than the single-agent treatment in tumor suppression. It should be noted that only naturally occurring inhibitors were selected for these experiments. The impact of minor dietary anutrients in cancer chemoprevention is also discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Levels and 75Se-labeling of specific proteins as a consequence of dietary selenium concentration in mice and rats.

Selenium-labeled proteins (SLP) distinct from glutathione peroxidase (GSH-PX) recently have been purified and partially characterized. Antisera to two SLP, a 56-kDa and a 14-kDa protein, were generated in rabbits and used to examine expression of these proteins as a consequence of dietary selenium concentration (0.02, 0.2, 2.0 ppm) in mice and rats. Additionally, the kinetics of 75Se labeling in plasma, liver, kidney, and mammary gland were examined over a 40-hr time period as a function of dietary selenium concentration. A plasma 57-kDa protein was labeled by 30 min after 75Se injection and reached maximum labeling by 4 hr. The cellular 56-kDa and 14-kDa proteins, as well as GSH-Px, labeled progressively over 40 hr starting between 1 and 4 hr after injection. In general, the 56-kDa and GSH-Px followed similar labeling patterns, whereas the 14-kDa protein was labeled less and was not labeled in discernible quantities until 40 hr. The extent of labeling of all proteins was inversely proportional to the dietary selenium concentration and was probably a reflection of different endogenous selenium body pools. The most important observation was generated by the immunoblot data. The amount of 56-kDa and 14-kDa proteins as detected and measured on immunoblots was not a function of dietary selenium concentration. This result suggests that the synthesis and maintenance of the 56-kDa and 14-kDa proteins are not selenium dependent, a characteristic which distinguishes the two proteins from GSH-Px. The single exception to the above results was the 40% decrease of liver 14-kDa protein concentration in carcinogen-treated rats fed 2.0 ppm of selenium. An organic selenium compound, selenobetaine, did not lead to a decrease under similar conditions. In 15 rat mammary tumors induced by 7,12-dimethylbenzanthracene and analyzed on immunoblots, the SLP-56 was undetected in 5 cases and appeared as two bands (56,000 Da, 50,000 Da) in 10 cases. This latter result raises the possibility that the expression of SLP-56 may be altered in mammary tumors as compared with normal mammary gland.

Animals↗
PubMed1990

Activity of methylated forms of selenium in cancer prevention.

The anticarcinogenic activity of selenium in animal models is well established. The active forms of selenium involved have not been identified to date, but conversion of selenium via hydrogen selenide (H2Se) to methylated forms such as dimethylselenide and trimethylselenonium ion is an important metabolic fate. By controlling the entry of selenium into various points within this pathway through selection of appropriate starting compounds, it is possible to pinpoint more closely the form(s) of selenium responsible for its anticarcinogenic activity. Selenobetaine in the chloride form [(CH3)2Se+CH2COOH] and its methyl ester are extensively metabolized in the rat to mono-, di-, and trimethylated selenides, largely bypassing the inorganic H2Se intermediary pool. The chemopreventive efficacy of these selenobetaines was determined at 1 and 2 ppm selenium supplemented in the diet throughout the duration of the experiment using the dimethylbenz(a)anthracene induced mammary tumor model in rats. There was a dose-dependent inhibitory response to both compounds, and they appeared to be slightly more active than selenite. These doses were without any adverse effects on the animals. Coadministration of selenobetaine with arsenite (5 ppm arsenic) enhanced the tumor-suppressive effect of selenobetaine, although arsenic by itself was totally inactive. Arsenite is known to inhibit certain steps in selenium methylation. The substantial prophylactic efficacy of methylated selenides and the enhancement by arsenite suggest that partially methylated forms of selenium may be directly involved in the anticarcinogenic action of selenium.

9,10-Dimethyl-1,2-benzanthracene↗