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C Ip

Publications and source records attributed to C Ip.

At least 109 records · Page 6Linked to original sources
PubMed1985

Isomeric fatty acids and tumorigenesis: a commentary on recent work.

This article critically reviews the existing, although limited, literature concerning trans fatty acids and tumorigenesis. Neither epidemiological nor experimental studies published to date have demonstrated any valid association between trans fatty acid ingestion and tumorigenesis. A recent study showed that under controlled conditions, a fat with a high content of trans fatty acids did not promote the development of mammary tumors induced in rats by 7,12-dimethylbenz[a]anthracene to any greater extent than did a comparable fat with a high content of cis fatty acids. In addition, in this study a high trans fat was less tumor promoting than was a blend of fats that simulated the dietary fat composition of the United States and had a lower level of trans fatty acids. Another study using comparable cis and trans fats demonstrated that the high trans fat did not affect the growth and metastasis of implanted mammary tumors in mice relative to the high cis fat. Also, two recent studies reported no significant difference in the development of induced colon tumors in rats fed diets high in cis or trans fatty acids. The results of these and other studies are consistent with the conclusion that trans fatty acids are not uniquely related to tumor development.

Animals↗
PubMed1985

Effects of selenium on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis and DNA adduct formation.

The purpose of the present investigation was to determine the effects of dietary selenium deficiency or excess on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary neoplasia in rats and to delineate whether selenium-mediated modification of mammary carcinogenesis was associated with changes in carcinogen:DNA adduct formation and activities of liver microsomal enzymes that are involved in xenobiotic metabolism. Female Sprague-Dawley rats were divided into three groups from weaning and were maintained on one of three synthetic diets designated as follows: selenium deficient (less than 0.02 ppm); selenium adequate (0.2 ppm); or selenium excess (2.5 ppm). For the DMBA binding and DNA adduct studies, rats were given a dose of [3H]DMBA p.o. after 1 month on their respective diets. Results from the liver and the mammary gland indicated that neither selenium deficiency nor excess had any significant effect on the binding levels, which were calculated on the basis of total radioactivity isolated with the purified DNA. Furthermore, it was found that dietary selenium intake did not seem to affect quantitatively or qualitatively the formation of DMBA:DNA adducts in the liver. Similarly, in a parallel group of rats that did not receive DMBA, the activities of aniline hydroxylase, aminopyrine N-demethylase, and cytochrome c reductase were not significantly altered by dietary selenium levels. Concurrent with the above experiments, the effect of dietary selenium intake on carcinogenesis was also monitored. Results of this experiment indicated that selenium deficiency enhanced mammary carcinogenesis only when this nutritional condition was maintained in the postinitiation phase. Likewise, an excess of selenium intake inhibited neoplastic development only when this regimen was continued after DMBA administration. In either case, deficient or excess selenium at the time of carcinogenic insult failed to produce a significant effect on subsequent tumor yield, if selenium intake was returned to normal during the proliferative phase of tumor growth. Based on the results of these studies, it is suggested that selenium-mediated modification of mammary tumorigenesis is not exerted via alterations in carcinogenic initiation (i.e., metabolism or DNA adduct formation).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Requirement of essential fatty acid for mammary tumorigenesis in the rat.

In an attempt to determine the requirement of essential fatty acid for dimethylbenz(a)anthracene-induced mammary tumorigenesis, rats were fed diets containing different levels of linoleate: 0.5, 1.1, 1.7, 2.2, 3.5, 4.4, 8.5, or 11.5%. Each diet contained 20% of fat by weight, with varying amounts of coconut oil and corn oil added to achieve the desired levels of linoleate. Mammary tumorigenesis was very sensitive to linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary linoleate. Regression analysis indicated that a breakpoint occurred at 4.4%, beyond which there was a very poor linear relationship, suggesting the possibility of a plateau. From the intersection of the regression lines in both the upper and lower ranges, the level of linoleate required to elicit the maximal tumorigenic response was estimated to be around 4%. The differences in tumor yield could not be correlated with changes in prostaglandin E concentration in the mammary fat pads of normal animals maintained on similar diets, suggesting that linoleate may act by some other mechanism to stimulate mammary tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Selenium inhibition of chemical carcinogenesis.

In this article I review the work of our laboratory concerning the relationship between dietary Se intake and susceptibility to mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in female rats. The effect of graded levels of Se in the diet was investigated, ranging from deficiency to excessive supplementation that produced marginal toxicity in the animals. In addition, the interdependence between Se status and fat intake was also explored. Further experiments were aimed at defining the role of Se in the initiation and promotion phases of chemical carcinogenesis. In view of the biochemical function of Se as an antioxidant, the chemopreventive efficacy of Se was compared to that of vitamin E in conjunction with their ability to inhibit lipid peroxidation. Results of this study indicated that the antitumorigenic activity of Se could not be accounted for by suppression of tissue peroxidation, although an environment with a lower oxidant stress might enhance the potency of Se in protecting against cancer. The possible mechanisms of action of Se based on the observations and characteristics of several tumor models are briefly discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Comparative effects of antioxidants on enzymes involved in glutathione metabolism.

The present study was designed to examine changes in glutathione metabolism in the liver of mice as influenced by supplementation of their diet with 1 of 4 antioxidants: butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E and selenium. In addition to determination of the acid-soluble thiol levels, 5 different enzymes involved with glutathione utilization and synthesis were measured: glutathione transferase, gamma-glutamyl transpeptidase, selenium-dependent glutathione peroxidase, gamma-glutamylcysteine synthetase and glutathione reductase. All 4 antioxidants produced significant increases in glutathione transferase activity, with BHA and BHT being much more effective than the other two. With the exception of vitamin E, BHA, BHT and selenium all resulted in a slight enhancement in the activity of glutathione reductase as well as in the acid-soluble thiol level. On the other hand, the induction of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase was responsive to only vitamin E and selenium supplementation, respectively. Although the influence of each of these antioxidants in glutathione metabolism appears to be specific and somewhat compartmentalized, the overall impression is that of an increased capacity for glutathione-conjugate formation and recovery of reduced glutathione. These biochemical changes in glutathione metabolism may be relevant to the anticarcinogenic effects observed with BHA, BHT and selenium.

Animals↗
PubMed1984

Similarity between trans fat and saturated fat in the modification of rat mammary carcinogenesis.

Commercial hydrogenation of vegetable oils results in the introduction of trans fatty acids. In the present study, we have investigated the effect of feeding a fat which contained approximately 38% trans isomers (designated trans fat) on the induction of mammary tumors by dimethylbenz(a)anthracene in rats. The corresponding control fat (designated cis fat), which had a similar fatty acid composition, consisted of only cis isomers. Since both the trans and cis fats were rather saturated, a comparison was also made between these 2 types of fat and corn oil, which contains about 60% linoleic acid (C18:2). Each fat was present in the diet at 2 levels, 5 and 20% by weight. Although rats fed the 20% trans fat or cis fat diets had a slightly higher tumor incidence and yield than did those on the corresponding 5% fat control diets, the difference was not statistically significant. In contrast, rats fed the 20% corn oil diet developed a much greater number of tumors than did rats fed a diet containing only 5% corn oil. Further analysis of the data showed that diets containing either trans fat or cis fat were much less effective than were the corn oil diets in promoting the development of mammary neoplasia at either the 5 or 20% level. Our results thus suggest that trans fat behaves very much like a saturated fat in the modification of mammary tumorigenesis. A determination of the fatty acid content of the mammary fat pad indicated that its composition generally reflected the dietary fatty acid intake, with the incorporation of trans isomers into the mammary tissue found to be dependent on the quantity of trans fat in the diet.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats.

The present study showed that vitamin E, although ineffective by itself, was able to potentiate the ability of selenium to inhibit the development of mammary tumors induced by dimethylbenz(a)anthracene (DMBA) in rats. Animals were maintained on a high-polyunsaturated fat (20% corn oil) diet in order to increase the degree of oxidant stress; additional selenium and/or vitamin E were present at a concentration of 2.5 and 1000 mg/kg of diet, respectively. It should be noted that rats tolerated these levels of supplementation very well with no obvious undesirable effect. Furthermore, our results indicated that vitamin E facilitated the anticarcinogenic action of selenium only when it was present during the proliferative phase. We then proceeded to examine whether DMBA administration would lead to any persistent damage in tissue peroxidation or changes in activities of enzymes associated with peroxide metabolism. It was found that DMBA resulted in an acute but modest increase in lipid peroxidation at 24 hr after carcinogen treatment. This perturbation was only of a transient nature. By comparing the response in a target tissue (mammary fat pad) and a non-target tissue (liver), it can be inferred that DMBA may have a differential effect on the degree of oxidant stress. The antagonistic effect of selenium and vitamin E in suppressing lipid peroxidation was then evaluated. Several conclusions can be drawn regarding the antioxidant potency of these agents in conjunction with their efficacies in cancer prevention. First, although vitamin E is a more effective antioxidant than selenium, it is apparent that systemic suppression of lipid peroxidation by vitamin E subsequent to a carcinogenic insult is not sufficient to inhibit tumor formation. Vitamin E supplementation increases significantly the microsomal hydroperoxidase activity. At the present time, it is unclear what role, if any, this enzyme plays in the synergistic effect of vitamin E and selenium in the inhibition of tumorigenesis. Secondly, the anticarcinogenic action of high levels of selenium is not related to its biochemical function in the regulation of the selenium-dependent glutathione peroxidase. The explanation for this is that the enzyme is already operating at near maximal capacity under normal physiological conditions. Additional selenium will not further increase its activity, since the enzyme protein becomes the limiting factor. Finally, vitamin E may be able to provide a more favorable climate against oxidant stress, thereby potentiating the action of selenium via some other mechanism.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Dietary vitamin E intake and mammary carcinogenesis in rats.

Using the dimethylbenz[a]anthracene-induced mammary tumor model, the present study demonstrated that a low vitamin E intake (7.5 mg/kg of diet) had minimal effect on carcinoma development in rats fed a 5% stripped corn oil diet, but resulted in a marked enhancement in tumor incidence and yield in those rats fed a 25% stripped corn oil ration. Control animals in this experiment received an adequate supply of vitamin E (30 mg/kg as DL-alpha-tocopheryl acetate). Thus, the effect of vitamin E deficiency on mammary carcinogenesis was accentuated in rats maintained on a high polyunsaturated fat diet, an observation similar to that of selenium deficiency which was reported by the author in a previous publication. In view of the biochemical interaction between vitamin E and selenium as endogenous antioxidants, another experiment was conducted to determine whether supranutritional supplementation of vitamin E (1000 mg/kg) was able to block the enhancement in mammary tumorigenesis due to selenium deprivation. Results of this experiment indicated that vitamin E excess failed to overcome the augmented tumor yield in selenium-deficient rats, nor did it provide any protection in rats that received an adequate supply of selenium. In summary, vitamin E deficiency may increase the risk of neoplastic development, especially when coupled with a high polyunsaturated fat intake; however, a high vitamin E supplementation does not seem to have any prophylactic effect on tumorigenesis by itself.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Interaction of dietary fat and the thymus in the induction of mammary tumors by 7,12-dimethylbenz(a)anthracene.

The interaction of dietary fat and the thymus in the induction of mammary tumors by dimethylbenz(a)anthracene has been examined in female Sprague-Dawley rats. In these experiments, rats fed diets of 0.5% (low fat), 5% (normal fat), or 20% (high fat) corn oil from weaning (21 days of age) were thymectomized or sham thymectomized at 35 days of age and were given 5 mg of dimethylbenz(a)anthracene at 55 days of age. Thymectomy exerted a protective effect in rats fed low and normal fat diets, and this was not reversed by Thymosin Fraction V. In high fat-fed rats, tumorigenesis was increased compared to the low fat groups, and in addition, the protective effect of thymectomy was absent. This differential effect of thymectomy could not be explained on the basis of changes in prolactin concentration, since prolactin levels were decreased in all dietary groups. Neither diet nor thymectomy affected corticosterone levels or the estrus cycle of mature rats. Peripheral blood lymphocytes were, however, decreased by both thymectomy and increasing the fat content of the diet. It is hypothesized that the promoting effect of dietary fat on dimethylbenz(a)anthracene-induced mammary tumorigenesis is mediated via the immune system, although a role for the endocrine system still cannot be ruled out.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Free amino acid pools of rodent mammary tumors.

Intracellular pools of free amino acids were compared individually in mammary tumors of Wistar Furth and Sprague-Dawley rats and C3H and DBA/2 mice. Of 11 transplantable and 7,12-dimethylbenz[a]anthracene-induced adenocarcinomas of the rat, all nonmetastasizing tumors could be distinguished from metastasizing tumors by the accumulation of high glutamine pools and significant-to-high cystathionine pools. In primary mammary tumors of C3H mice and transplanted mammary tumors of DBA/2 mice, intracellular free arginine was frequently below that of the circulating plasma level and approached that in the arginine-destroying organ, the liver. Arginine pool depletion was also noted in normal mammary tissue, particularly in the actively lactating mouse. Individual rat or mouse mammary tumors also contained high levels of taurine, beta-alanine, and gamma-aminobutyric acid, which, like cystathionine, are distinctive for or are enriched in neural tissue. None of these pool enrichments were characteristic of normal rat or mouse mammary tissue. Free hydroxyproline was low in primary induced rat mammary tumors and higher in transplanted mammary tumors and in normal lactating mammary glands, particularly in the mouse. In contrast, the hydroxyproline residues of collagen, taken as an index of mesenchymal cell contribution, were very low in all tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Dietary selenium intake and growth of the MT-W9B transplantable rat mammary tumor.

The present study reports the effect of dietary selenium deficiency and supplementation on the growth of the transplantable MT-W9B mammary tumor in female Wistar-Furth rats. Supplementation of the diet with 2 ppm of selenium inhibited tumor growth and reduced the final tumor weight by approximately 50% compared to the control rats receiving 0.1 ppm of selenium. The inhibitory response was selective, without inducing any weight loss in the animals. On the other hand, selenium deficiency (less than 0.02 ppm) had no influence on the growth of this tumor.

Animals↗
PubMed1981

Neoplastic growth of carcinogen-treated mammary transplants as influenced by fat intake of donor and host.

Female Wistar-Furth rats were fed either a high-fat (HF) or a low fat (LF) diet from weaning. The HF and LF diets contained 20% and 0.5% corn oil, respectively. Mammary gland explants from 50-day-old rats of both dietary groups were exposed to dimethylbenz[a]anthracene in organ culture before grafting to HF- or LF-hosts. A total of 4 groups were involved: LF leads to LF, HF leads to LF, LF leads to HF, and HF leads to HF, where the designations before and after the arrow describe the dietary treatment of the donor and host, respectively. Final tumor incidences were as follows: 28%, 20%, 72% and 76%, presented in the order of the above 4 groups. Tumors also appeared earlier in the HF-hosts. Results of this experiment indicate that regardless of the nutritional status of the donor, it was the fat intake of the host that governed the subsequent neoplastic growth of transformed cells, suggesting that the action of fat is primarily exerted at the promotional stage of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Lack of effect of dietary fat on the growth and estrogen sensitivity of the MT-W9B transplantable mammary tumor.

The growth rate and the estrogen responsiveness of the MT-W9B transplantable mammary tumor were examined in female Wistar-Furth rats which were fed diets containing either 0.5% or 20% fat for 50-60 days. Estrogen responsiveness was determined by changes in progesterone receptor concentration in response to estrogen deprivation and replacement. This parameter was also measured in the uterus as a normal tissue control. Progesterone receptor levels in tumor and uterus were reduced by ovariectomy to a similar extent in rats fed either low-or high-fat diets. In addition, estrogen induction of the progesterone receptor in ovariectomized rats was not altered by dietary fat intake. Growth of the MT-W9B tumor was not affected by either diet or endocrine manipulation. Uterine growth, as expected, was dependent on estrogen status, but both the growth and its sensitivity to estrogen manipulation were independent of the fat content of the diet. These data suggest that dietary fat does not influence the sensitivity of normal or neoplastic tissue to estrogen action.

Animals↗
PubMed1981

Anticarcinogenic effect of selenium in rats treated with dimethylbenz[a]anthracene and fed different levels and types of fat.

The present investigation reports the effect of selenium supplementation on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats fed either a 5% or a 25% corn oil diet. A reduction in tumorigenesis in both groups was observed with 2.5 p.p.m. of dietary selenium. Selenium supplementation also inhibited the development of hyperplastic alveolar nodules in the mammary gland subsequent to DMBA treatment. In addition, the appearance of mammary neoplasia was reduced by selenium in rats fed a high-saturated fat diet (coconut oil), indicating that the type of fat consumed did not influence the antitumorigenic effectiveness of selenium. The lack of a correlation between the anticarciongenic efficacy of selenium and its ability to suppress lipid peroxidation in the mammary tissue of rats fed either a high-saturated fat or a high-unsaturated fat diet suggests that the inhibitory action of selenium is probably not mediated by its antioxidant function in lipid metabolism

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Chemoprevention of mammary tumorigenesis by a combined regimen of selenium and vitamin A.

Mammary tumorigenesis induced in rats by 7,12-dimethylbenz[a]anthracene was markedly suppressed by combined dietary supplementation with sodium selenite and retinyl acetate; final tumor yield was reduced to 8% of control as compared with 51% and 36%, respectively, for selenium and retinyl acetate alone. A continuous intake of both agents was necessary to sustain the chemopreventive effect.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Enhancement of mammary tumorigenesis by dietary selenium deficiency in rats with a high polyunsaturated fat intake.

The effect of selenium depletion on mammary tumorigenesis following dimethylbenz[a]anthracene administration was examined in female Sprague-Dawley rats that were fed different levels and types of fats. Four basal diets deficient in selenium were used: (a) 1% corn oil; (b) 5% corn oil; (c) 25% corn oil; and (d) a high saturated fat diet containing 1% corn oil and 24% hydrogenated coconut oil. The comparable selenium-adequate diets were obtained by adding 0.1 ppm of selenium to each of the basal diets. In animals that received an adequate supplement of selenium, an increase in fat intake was accompanied by an increased tumor incidence when corn oil was used in the diets. A high saturated fat ration, on the other hand, was much less effective in this respect. Only in those rats that were maintained on a high polyunsaturated fat diet (25% corn oil) did selenium depletion result in a further increase in tumor incidence and tumor yield. Such an augmentation was not observed in animals given either a 1 or a 5% corn oil ration or a diet rich in saturated fat. Regardless of selenium status, almost all of the tumors found were adenocarcinomas. An enhancement of tumorigenesis as a result of selenium deficiency in rats fed the 1% corn oil regimen was detected provided a high dose of dimethylbenz[a]anthracene was used, suggesting that alterations in dimethylbenz[a]anthracene metabolism might be involved under this condition. The antioxidant property of selenium is discussed as a possible mechanism by which selenium protects against tumorigenesis, especially in animals with a high polyunsaturated fat intake.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Serum estrogens and estrogen responsiveness in 7,12-dimethylbenz[a]anthracene-induced mammary tumors as influenced by dietary fat.

The effect of dietary fat on mammary tumor incidence, estrogen-binding capacity as related to the hormone dependency of the tumors, and circulating estrogen levels in Sprague-Dawley rats given an oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Rats were fed diets consisting of 0.5, 5, or 20% corn oil starting at weaning and were administered 5 mg DMBA at 50 days of age. Tumor incidences were 13, 46, and 75% for the groups given 0.5, 5, and 20% fat, respectively, when the experiment was terminated 20-22 weeks later. Serum estradiol, measured at proestrus at 50 days of age and at the end of the experiment, was slightly depressed at both time points in rats fed the 0.5% fat diet but was similar in the other 2 groups. Serum estrone levels were not significantly different at either time point. Estrogen receptor levels in the tumor were the same in the groups given 5 and 20% fat but were lower in the group given 0.5% fat. No difference was detected in the progesterone receptor concentrations. Furthermore, most (approximately 70%) of the tumors in all 3 dietary groups regressed in response to ovariectomy, which suggested that dietary fat has very little influence on the estrogen dependence of the tumor. This observation suggested that fat intake does not result in any intrinsic difference in the biochemical action of estrogen.

9,10-Dimethyl-1,2-benzanthracene↗