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Biomedical subjects

M M Ip

Publications and source records attributed to M M Ip.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effects of high dietary fat on the growth and development of ovarian-independent carcinogen-induced mammary tumors in rats.

This study examined the influence of high dietary fat intake on the development of ovarian-independent mammary tumors in both vehicle-treated controls and rats made deficient in estrogen and prolactin during tumor induction. The majority of 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumors in rats are dependent on estrogen and prolactin for growth, and suppression of prolactin and estrogen at the time of tumor initiation causes a reduction in tumor incidence and increase in tumor latency. However, the majority of mammary tumors which do develop in these animals exhibit ovarian-independent growth. Sprague-Dawley rats were given 7.5 mg DMBA p.o. at 57 days of age. Starting 1 day prior to and continuing for 7 days after DMBA administration, rats were given daily injection of vehicle or the combination of tamoxifen (20 micrograms/rat) plus bromocryptine (5 mg/kg). At the end of drug treatment, rats in each treatment group were equally divided and placed on normal fat (5% corn oil) or high fat (20% corn oil) diets for the duration of the experiment. Vehicle-treated rats were ovariectomized 27 wk and drug-treated rats 47 wk after DMBA administration to determine tumor ovarian dependency. Vehicle-treated rats fed high fat diets showed significant increases in mammary tumor incidence and number as compared to similarly treated rats fed a normal fat diet, with approximately 80% of the tumors in each group being ovarian dependent. Likewise, tamoxifen-bromocryptine-treated rats fed a high fat diet showed a significant enhancement in mammary tumor number, although not incidence, as compared to similarly treated rats fed a normal diet. Tumors in these drug-treated groups displayed essentially the same incidence of ovarian dependence (23%). Tamoxifen-bromocryptine-treated groups displayed a 2-fold increase in latency of tumor appearance as compared to vehicle-treated controls; however, this long latency was not reduced when these rats were fed a high fat diet. These results demonstrate that high dietary fat stimulates ovarian-dependent and -independent mammary tumorigenesis in rats but does not influence the hormonal responsiveness of these tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Comparative effects of different animal and vegetable fats fed before and during carcinogen administration on mammary tumorigenesis, sexual maturation, and endocrine function in rats.

The purpose of this investigation was to determine whether diets high in animal or vegetable fat affected mammary tumorigenesis when fed to rats only prior to and during the initiation phase of carcinogenesis. Weanling 21-day-old female Sprague-Dawley rats were divided into different dietary treatment groups and were allowed to feed and libitum on one of the following diets: 5% (normal fat) corn oil; 20% (high fat) corn oil; 20% palm oil; 20% beef tallow; or 20% lard. At 52 days of age, all rats were given p.o. 7.5 mg 7,12-dimethylbenz(a)anthracene (DMBA). One week following DMBA administration, all rats were switched to the 5% corn oil control diet and were maintained on this diet for the duration of the experiment. Rats fed a 20% lard diet during the treatment period showed a significant increase in mammary tumor incidence and number 19 weeks after DMBA administration, when compared to all other dietary treatment groups. Rats fed a 20% beef tallow diet during this same time period also demonstrated enhanced mammary tumor development, during the 10- to 19-week time period after DMBA. Mammary tumor development in rats fed 20% corn oil or palm oil diets during this treatment period was similar to that of normal fat controls. Estrogens are potent stimulators of mammary tumor growth and development in rats. Because mammary tumorigenesis was enhanced in rats fed high animal, but not vegetable fat diets, it was possible that estrogens present in animal fat might be responsible for this stimulation. Further studies demonstrated however, that increased mammary tumorigenesis in rats fed diets high in animal fat could not be explained on the basis of endocrine stimulation. Average day of vaginal opening for all groups fed 20% fat diets was similar and occurred earlier than in normal fat controls. In addition, 50- to 65-day-old rats in the different dietary treatment groups showed no differences in basal or surge levels of serum prolactin, luteinizing hormone, or estradiol. Rat diestrus uterine weight also showed no significant differences among dietary treatment groups. Thus diets containing high levels of animal fat caused little if any increased estrogenic activity in rats. In conclusion, high dietary intake of lard and beef tallow, but not vegetable fat, fed from weaning until only 1 week after DMBA administration, significantly enhances mammary tumorigenesis in rats. The mechanism(s) by which animal fat induces this stimulation is not clear, but it does not appear to result from endogenous or exogenous endocrine stimulation.

Animals↗
PubMed1986

Antitumor efficacy in rats of CGP 19984, a thiazolidinedione derivative that inhibits luteinizing hormone secretion.

The antitumor efficacy and the hormonal effects of the thiazolidine-dione derivative (sodium methyl((-3-methyl-2- ([5-methyl-3-(2-methylallyl)-4-oxo-2 thiazolidinyliden]hydrazono)-4-oxo-5-thiazolidinyl)) phosphate, CGP 19984, have been studied in in vivo rat prostatic and mammary cancer models. CGP 19984 significantly inhibited growth of the androgen-dependent Dunning R3327 rat prostate adenocarcinoma. Concomitant with tumor inhibition, a significant decrease in circulating luteinizing hormone and testosterone levels was observed, suggesting that the antitumor effects of drug treatment resulted primarily from inhibition of luteinizing hormone release and subsequently decreased testosterone synthesis. Drug treatment had little effect on serum prolactin or corticosterone levels. Animals showed no adverse effects from CGP 19984 except for a modest loss of body weight. In female rats, growth of the estrogen-independent MTW-9B rat mammary tumor was also inhibited by CGP 19984 and uterine weight and tumor progesterone receptor levels were reduced. The latter suggests that CGP 19984 treatment decreases circulating estrogen in female rats. However, the inhibitory effect of CGP 19984 on the growth of the MTW-9B tumor does not appear to be mediated by the action of the drug to lower estrogen levels, since this tumor is not dependent on estrogen for growth, and lower doses of CGP 19984 were found to be equally effective in reducing uterine weight, but had no antitumor activity. The ability of CGP 19984 to suppress gonadal function and to inhibit tumor growth suggests that this drug may have potential clinical application in the treatment of both hormone-dependent and -independent prostate and breast cancers.

Adenocarcinoma↗
PubMed1985

Regulation of rat natural killing. I. Inhibition of cytolysis and activation by protein synthesis inhibitors.

Rat splenic natural killer (NK) cell activity against 51Cr-labeled YAC-1 or TMT-081 tumor cells can be augmented by culturing at 37 degrees C for 18 h. The protein synthesis inhibitors, cycloheximide and emetine, inhibited such NK activation and also inhibited NK lysis when added directly to the NK assay. Both drugs also inhibited conjugation of effector cells to target cells. The inhibitory effect of cycloheximide on both the NK lysis and NK activation was reversible while that of emetine was irreversible. Both agents were able to inhibit 3H-amino acid incorporation at the concentrations that inhibited NK activity and activation. Culture-activated NK cells were found to be less susceptible to inhibition by cycloheximide and emetine.

Animals↗
PubMed1985

Binding of the glucocorticoid receptor complex to the nucleosomal core in the P1798 mouse lymphosarcoma.

Binding of the glucocorticoid receptor complex to nucleosomes has been studied using the mouse P1798 lymphosarcoma. Cells were incubated with [3H]triamcinolone acetonide (TA), and nuclei prepared and digested with 3 different concentrations of micrococcal nuclease. After fractionation with EDTA and NaCl, it was observed that [3H]TA bound with similar specific radioactivity to mononucleosomes containing both core and linker DNA, of 183 +/- 5, and 168 +/- 4 base pair lengths, respectively, as well as to core size DNA, of 148 +/- 3 base pair length, suggesting that the glucocorticoid receptor bound to the core portion of the nucleosome. Steroid binding was found to be associated with regions of the nucleosome that were depleted in histone H1 and enriched in high mobility group (HMG) proteins 1 and 2; only negligible binding was noted in nucleosomes enriched in histone H1 and depleted in HMG proteins. In addition to binding to core nucleosomes, the glucocorticoid receptor complex was also shown to bind to a fraction sedimenting at 5-6 S on sucrose gradients characterized by subnucleosome and mononucleosome size DNA, as well as by core histones. While binding of the steroid receptor complex to linker regions of the nucleosome cannot be ruled out, this data would appear to present the first concrete evidence that glucocorticoid binding, at least in the P1798 lymphosarcoma, is to core nucleosomes. Some caution in interpretation of the results is indicated, however, on 2 points: (1) receptor redistribution during nuclease digestion cannot be ruled out; (2) only the binding of a small proportion of the steroid receptor complex may be physiologically relevant.

Animals↗
PubMed1985

Effect of a high-protein-low-carbohydrate diet on toxicity and antitumor activity of 5-fluorouracil in mice.

The effect of different levels of dietary protein on 5-fluorouracil (FUra) toxicity and antitumor activity was assessed in female (BALB/c X DBA/2Ha)F1 (CDF1) and BALB/c mice bearing the P1798 lymphosarcoma. In the toxicity experiments, CDF1 mice were fed diets containing 5% [low protein (LP)], 20% [normal protein (NP)], or 60% [high protein (HP)] casein for 22 days and were then given a single ip injection of 275 mg FUra/kg. As determined by effects on the white blood cell count and by changes in body weight, FUra was least toxic in mice fed the HP diet. Moreover, mortality was 77.0, 42.9, and 11.4% for mice fed the LP, NP, and HP diets, respectively. In the antitumor studies, BALB/c mice bearing the P1798 lymphosarcoma were fed one of the 3 diets starting 5 days after transplant. Mice were given injections of 50 mg FUra/kg or the vehicle control on days 14 and 15 after transplant. As measured by tumor weights on day 16, FUra was least effective in mice fed the LP diet and most effective in mice fed the NP and HP diets. Survival time of mice given injections of FUra on days 14 and 15 was increased when compared to the survival time of control mice, but no difference in the percent increase in survival time was noted among the 3 dietary groups. If mice were given two cycles of FUra therapy (days 14 and 15 and days 20 and 21), mice fed the HP diet survived significantly longer than did mice fed the LP or NP diet. These data demonstrate that the feeding of an HP diet markedly decreases the toxicity of FUra while preserving or actually enhancing the antitumor effect.

Animals↗
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↗
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

Effect of the prostaglandin synthetase inhibitor indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat.

The effect of the prostaglandin synthetase inhibitor indomethacin on the dietary fat enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis has been examined in female Sprague-Dawley rats. Rats were fed either a normal-fat or high-fat diet (5 or 18% corn oil, respectively) with or without 0.004% indomethacin, starting 3 days after a single intragastric intubation of 5 mg 7,12-dimethylbenz(a)anthracene. Results of this experiment demonstrated that indomethacin completely blocked the stimulatory effect of fat on tumorigenesis, as measured by a decreased tumor incidence, a decreased number of tumors per group, a decreased tumor size, and an increased latency. No effect of indomethacin was observed in rats fed the normal-fat diet. These data suggest that at least part of the stimulatory effect of polyunsaturated fat on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis may be mediated through an increased synthesis of prostaglandins.

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

Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat.

The effect of androgen on the levels of the cytosol progesterone receptor was examined in the transplantable rat mammary tumor MT-W9B and in the normal uteri of inbred WF rats. Progesterone receptor levels were barely detectable in tumors grown in male WF rats but were increased after castration or administration of 17 beta-estradiol. Both effects were blocked by testosterone. In tumors grown in intact female rats, both testosterone and dihydrotestosterone decreased progesterone receptor levels in a dose-dependent manner, and testosterone completely blocked the estradiol-induced increase in progesterone receptor levels in tumors from ovariectomized rats. The inhibitory effect of testosterone in female rats was blocked by the antiandrogen flutamide, suggesting an androgen receptor-dependent mechanism. Neither dihydrotestosterone nor testosterone had any effect on basal levels of progesterone receptor in tumors from ovariectomized rats. In uterus, up to 5 mg dihydrotestosterone/kg did not affect progesterone receptor levels, and a dose of 5 mg/kg was also uterotropic. This fact plus the finding that testosterone only partially blocked the estradiol-induced increase in uterine progesterone receptor levels suggested stimulation of different cell types by testosterone and estradiol. This did not appear to be the case in the tumor, however. Androgen is suggested to act as a negative modulator of progesterone receptor levels, which might have clinical relevance in terms of hormone therapy of breast cancer.

Androgens↗
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

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

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

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↗
PubMed1981

Dichotomous effects of tamoxifen on a transplantable rat mammary tumor.

The effect of the antiestrogen tamoxifen on growth of the transplantable autonomous mammary tumor MTW-9B was compared with its effects on progesterone and estrogen receptor levels. Growth of the tumor was similar in intact rats, ovariectomized rats, or ovariectomized rats given estradiol, in both the presence and the absence of tamoxifen. Progesterone receptor levels, however, were reduced by ovariectomy and restored by estrogen administration. Tamoxifen antagonized this effect of estrogen, although when administered by itself to ovariectomized rats it acted as an agonist, since progesterone receptor levels were induced. Cytosol estrogen receptor was depleted by tamoxifen in both intact and ovariectomized rats. In uterus from the same animals, tamoxifen also showed both antagonist and agonist properties, although here too there was an apparent dissociation between effects on growth and progesterone receptor levels. We conclude from these experiments that: (a) the estrogen receptor complex may be acting at more than one site on the genome; and (b) regulation of progesterone receptor levels by estrogen (or tamoxifen) does not necessarily predict sensitivity of tumor growth to antiestrogens.

Animals↗
PubMed1980

Inhibition of mammary tumorigenesis by a reduction of fat intake after carcinogen treatment in young versus adult rats.

The present study demonstrates that a reduction of fat intake after dimethylbenz[alpha]anthracene (DMBA) administration to female Sprague--Dawley rats leads to an inhibition of mammary tumorigenesis. Animals were fed a 20% fat diet from weaning and were transferred to a 0.5% fat diet 0, 2, 4, and 6 weeks after carcinogen treatment. In rats given DMBA at 50 days of age, the following observations were obtained: (a) tumor incidence, as well as tumor yield, was decreased when the transfer to a low fat diet was initiated up to 4 weeks after DMBA; (b) regardless of fat intake, over 90% of tumors developed in all dietary groups were adenocarcinomas. This was in contrast to rats given DMBA at 150 days of age. In this case (a) a 50% reduction in tumor incidence was apparent when the low fat diet was introduced even 6 weeks after DMBA intubation; and (b) more benign lesions were found and an association between a reduced risk of carcinogenesis and a lower ratio of adenocarcinoma to fibroadenoma seems to exist. Thus, the data demonstrate that the rats were less vulnerable to delays in reduction of fat intake on subsequent inhibition of mammary tumorigenesis than if they were exposed to the carcinogen at an older age.

9,10-Dimethyl-1,2-benzanthracene↗