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Biomedical subjects

C Ip

Publications and source records attributed to C Ip.

At least 127 records · Page 7Linked to original sources
PubMed1981

Factors influencing the anticarcinogenic efficacy of selenium in dimethylbenz[a]anthracene-induced mammary tumorigenesis in rats.

The present study was designed to investigate the effect of selenium supplementation on dimethylbenz[a]anthracene-induced mammary tumorigenesis in female Sprague-Dawley rats fed either a 5 or 25% corn oil diet, denoted as low fat (LF) or high fat (HF), respectively. Selenium supplementation of LF and HF diets were begun at 21 days of age. In Experiment 1, rats (50 days of age) were given 5 mg of dimethylbenz[a]-anthracene p.o. and were supplemented with 0.1 (adequate level), 0.5, 1.5, and 2.5 ppm of selenium (as sodium selenite) in the diet. The total number of tumors found were as follows (30 rats/group): 26, 23, 19, and 10, respectively, in the LF group; and 65, 66, 41, and 21, respectively, in the HF group. In experiment 2, rats (50 days of age) were given 10 mg of dimethylbenz[a]anthracene, and selenium was added to the diets at 0.1, 2,5, and 5.0 ppm. Tumor yields were found to be 71, 32, and 15, respectively, in the LF group and 135, 85, and 46, respectively, in the HF group. There was also a trend towards a longer latency period of tumor appearance with selenium supplementation. In conclusion, high dietary selenium levels are able to protect against mammary tumorigenesis, but rats on a HF diet still develop more tumors than those on a LF diet at comparable selenium supplementation.

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

Prophylaxis of mammary neoplasia by selenium supplementation in the initiation and promotion phases of chemical carcinogenesis.

The present study was designed to determine the chemopreventive effect of dietary selenium supplementation in the initiation or promotion phase of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in rats fed a high-fat diet. Control animals received 0.1 ppm of selenium (as sodium selenite), while experimental groups were supplemented with 5 ppm of selenium for various periods of time: -2 to +24, -2 to +2, +2 to +24, +2 to +12, +12 to +24, and -2 to +12. The time of 7,12-dimethylbenz[a]anthracene administration (50 days of age) was taken as Time 0; minus and plus signs represent the time in weeks before and after 7,12-dimethylbenz[a]anthracene administration, respectively. The following conclusions were drawn from the results: (a) selenium can inhibit both the initiation and promotion phases of carcinogenesis; (b) a continuous intake of selenium is necessary to achieve maximal inhibition of tumorigenesis; (c) the inhibitory effect of selenium in the early promotion phase is probably reversible; and (d) the efficacy of selenium is attenuated when it is given long after carcinogenic injury. In addition, the present investigation also assessed the effectiveness of selenium in inhibiting the reappearance of mammary tumors that had regressed after ovariectomy. By supplementing tumor-bearing animals with 5 ppm of selenium in the diet immediately after endocrine ablation, it was found that tumors reappeared at a slower rate compared to the controls. The data suggested that selenium is not only effective in chemoprevention but can also be used as an adjuvant chemotherapeutic agent.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Changes in tissue and serum sialyltransferase activities as related to proliferation and involution of the rat mammary gland.

This study, which was performed on rats, demonstrates that the changes in both mammary tissue and serum sialyltransferase activities parallel the growth of the mammary gland, as measured by the DNA content of the tissue. An increase in the specific activity of the enzyme was evident during rapid cellular proliferation, followed by a return to basal values upon cessation of growth and involution of the glands. This pattern occurred under 3 different experimental conditions: (a) pregnancy-lactation-weaning, (b) pseudopregnancy induced by stimulation of cervix, and (c) daily administration of 1 microgram estradiol and 3 mg progesterone to promote mammary development equivalent to that of late pregnancy and subsequent decay of mammary gland after withdrawal of hormonal treatment. Although it is difficult to differentiate whether the increase in tissue sialyltransferase is dependent on hormonal stimulation or as a consequence of growth, the elevation in serum sialyltransferase seems to be closely related to the degree of cellular proliferation.

Animals↗
PubMed1980

Regulation of cyclic adenosine 3',5'-monophosphate in relation to growth of dimethylbenz[a]anthracene-induced mammary tumors in rats.

In this study, adenylate cyclase, phosphodiesterase and cyclic adenosine 3',5'-monophosphate (cAMP) levels were measured in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors with different growth characteristics in both intact and ovariectomized rats. Tumors were classified as growing, stable, or regressing over a 10-14-day period before excision. Regressing or static tumors had a higher cAMP concentration relative to tumors that were growing actively. This was due to high adenylate cyclase activity and low phosphodiesterase (both high and low Km) activities. Although estrogen deprivation resulted in a much greater rate of tumor regression than would occur spontaneously under normal conditions, the levels of adenylate cyclase, phosphodiesterases and cAMP were the same in tumors obtained from either intact or ovariectomized rats, when comparisons were made within the same category of tumor. These observations suggest that cAMP metabolism is independent of estrogen, since it is related to enhancement or retardation of growth rather than to the presence of absence of estrogen.

9,10-Dimethyl-1,2-benzanthracene↗
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↗
PubMed1980

Serum sialyltransferase and 5'-nucleotidase as reliable biomarkers in women with breast cancer.

Sialyltransferase and 5'-nucleotidase were measured in the sera of 135 women with breast cancer: 53 undergoing mastectomy for primary cancer and 83 receiving different modalities of palliative therapy for metastatic disease. The objective of this study was to determine whether these enzyme levels were associated with the extent of the disease and whether changes in these enzyme levels could be correlated with success or failure of treatment. Mastectomy caused a rapid fall of elevated enzyme levels to within the normal range in all patients with stage I breast cancer but not in those with stage II or III disease. In women with metastatic disease, elevated enzyme levels fell only in patients responding to treatment. Thus serum sialyltransferase and 5'-nucleotidase activities are reliable biomarkers of breast cancer activity, and serial measurement of these enzyme activities provides a useful tool for the monitoring of disease activity and success or failure of the treatment.

Adolescent↗
PubMed1980

Role of prolactin in the promotion of dimethylbenz[a]anthracene-induced mammary tumors by dietary fat.

Following 7,12-dimethylbenz[a]anthracene (DMBA) administration, increased tumor incidence and tumor yield were observed in intact rats fed a 20% corn oil diet compared to those fed a 0.5% corn oil diet. Elevated serum prolactin levels (determined at proestrus) were also found in the former group of animals. In order to delineate whether this was responsible for the promoting effect of dietary fat in DMBA-induced mammary carcinogenesis, rats fed these two diets were subjected to electrolytic lesion of the median eminence that resulted in higher circulating prolactin concentrations. Sham-operated animals were used as controls. Results showed that this endocrine manipulation increased the tumor incidence in the low-fat group nearly 3-fold, but it failed to elicit further enhancement in the high-fat rats. Although the serum prolactin level in the low-fat-lesioned rats was comparable to that in the high-fat-lesioned rats, the tumor incidence in the former group still lagged behind that in the latter (33.3 versus 70.4%). Thus, it can be concluded that, although increased circulating prolactin in rats fed the high-fat diet may be partly responsible for the higher tumor incidence, other factors besides prolactin may be involved in the promoting effect of dietary fat in mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Effect of partial hepatectomy and hydrocortisone administration on liver and serum sialyltransferase activities.

Partial hepatectomy of rats was followed by a rise in liver sialyltransferase activity. The maximum (2.5-fold increase) was reached on the third day after the operation, after which the level started to decline, returning to normal by day 6. Determination of serum sialyltransferase in these animals showed a parallel pattern. Daily injection of 5 mg hydrocortisone to adrenalectomized rats led to a maximal 3-fold elevation in liver sialyltransferase within 3 days, but failed to elicit any change in the corresponding enzyme in the serum. Results from these two experiments suggest that the elevations of sialyltransferase in the tissue and in the circulation are independently regulated.

Adrenalectomy↗
PubMed1978

Alterations in serum glycosyltransferases and 5'-nucleotidase in breast cancer patients.

We have measured sialyltransferase, galactosyltransferase, and fucosyltransferase as sell as 5'-nucleotidase in the serum of breast cancer patients. Serum sialyltransferase values in 65 normal healthy females ranged from 2.6 to 8.5 units, with a mean of 5.4. In 25 women with operable primary breast cancer, serum sialyltransferase levels were found to be between 6.2 and 15.4 units. Marked elevation of this enzyme level (range, 8.8 to 36 units) was observed in 48 patients with metastatic breast cancer. Galactosyltransferase and fucosyltransferase measurements, however, showed considerable overlap between the controls and the cancer patients. On the other hand serum 5'-nucleotidase and sialyltransferase in breast cancer patients showed very similar patterns. Thus, serum 5'-nucleotidase values in 44 normal females ranged from 11.4 to 23.2 units, whereas the levels found in 30 patients with metastasis were between 25 and 71.8 units. The tissue origin of abnormal levels of serum glycosyltransferases and 5'-nucleotidase was discussed in relation to their physiological significance as well as their role as markers for diagnosing early malignant breast neoplasm and for monitoring the extent of metastasis.

Breast Neoplasms↗
PubMed1977

The effect of diet fat on rat adipocyte glucose transport.

Rats were fed either a high fat diet (67% of calories as lard) or high glucose diet (67% of calories as glucose) for 7-8 days. Basal and insulin stimulated net uptake of D glucose (D-L) and 2 deoxy D glucose uptake by free fat cells of fat rats were depressed. Net transport of D glucose (D-L) by purified adipocyte plasma membranes of fat red rats was also diminished. Incubation of fat cells from glucose fed rats with insulin before homogenization for membrane preparation increased net D glucose transport by subsequently purified membranes in two experiments to a greater extent than in similar preparations from rat fed rats. These experiments suggest that fat feeding modifies the plasma membranes of fat cells so that both glucose transport and the stimulatory effect of insulin on the process are decreased.

Adipose Tissue↗
PubMed1977

Effect of adaptation to meal-feeding on insulin, glucagon and the cyclic nucleotide-protein kinase system in rats.

Diurnal changes in insulin, glucagon and the cyclic nucleotide-protein kinase system were examined in rats trained to eat a 2-hour daily meal and in control rats fed ad libitum. Sharp increases in both insulin and glucagon were observed in response to feeding in trained rats. However, throughout most of the rest of the day, the plasma concentrations of both hormones were lower in meal-fed than in control rats. In adipose tissue, diurnal changes in cyclic AMP concentration were inversely correlated with changes in plasma insulin concentration. In general, cyclic AMP concentrations were depressed and cyclic GMP elevated in adipose tissue of meal-fed rats compared with those fed ad libitum. Diurnal changes in cyclic GMP concentration tended to parallel those of cyclic AMP. Cyclic AMP-activated protein kinase was elevated in adipose tissue of meal-fed rats. However, with the exception of fasting rats, the percentage of the enzyme in the active form was decreased. In liver, there was no clear relation significant differenced were observed with the protein kinase. It can be concluded that the magnitude of the adaptive response of the cyclic nucleotide-protein kinase system to meal-feeding in rats is greater in adipose tissue than in liver.

Adaptation, Physiological↗
PubMed1976

Effect of p-chlorophenoxyisobutyrate on the antilipolytic action of insulin and insulin binding in isolated adipocytes.

The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum triglyceride levels in rats from the three dietary groups. The catecholamine-stimulated glycerol release was significantly depressed to a greater extent by insulin when the fat cells were obtained from rats given CPIB compared to those without drug treatment. The enhanced insulin sensitivity was, however, not accompanied by any changes in insulin binding to adipocytes. These two observations were found in cell preparations from rats fed any one of the diets, although differences among dietary groups could be detected. In an in vitro experiment, epinephrine-stimulated glycerol release was progressively inhibited by increasing concentrations of CPIB in the incubation medium. However, the antilipolytic response to an optimal concentration of insulin (100 muU/ml) was augmented in the presence of CPIB. Thus, it seems that CPIB can potentiate the action of insulin in inhibiting mobilization of free fatty acid from the adipose tissue, and the coordinated effect of both antilipolytic agents is important in lowering serum triglyceride concentration. The mechanism by which CPIB facilitates the effect of insulin is discussed.

Adipose Tissue↗
PubMed1976

Insulin binding and insulin response of adipocytes from rats adapted to fat feeding.

The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high glucose (G) diet. Both high and low affinity sites were influenced; the extent of the binding difference increased as increasing concentrations of insulin were present in the assay medium. Diet did not change hormone degradation on the capacity of phospholipase C to increase binding. Concanavalin A effects on fat cells were also decreased by L diet both in inhibition of insulin binding and its insulin-like effect on glucose oxidation. Spermine, which had no effect on insulin binding, also had a smaller insulin-like effect on glucose oxidation by L cells than by G cells. Serum insulin was significantly lower (30 +/- 3.7 muU/ml) in L than in G (43 +/- 3.1 muU/ml) groups. Dietary fat produces alterations in fat cells that decrease insulin binding as a part of a complex overall adaptation to the diet.

Adipose Tissue↗
PubMed1975

Protein synthesis in liver, muscle, and brain of rats fed a high tyrosine-low protein diet.

Effects of feeding rats a high tyrosine-low protein diet on protein synthesis in liver, muscle, and brain were investigated both in vitro and in vivo. Tissue tyrosine concentrations of rats consuming the high tyrosine diet for 7 days were substantially elevated; this was accompanied by severe growth retardation. In the livers of rats fed the high tyrosine diet for 6 days, polysomal profiles showed a shift toward heavier ribosomal aggregates, while in muscle and brain, extensive disaggregation of polysomes occurred. In an in vitro amino acid incorporating system, the activities of both the microsomal and pH 5 enzyme fractions isolated from the livers of the high tyrosine animals that had been fed the diet for 6 weeks were elevated. On the other hand, the capacity of muscle or brain ribosomal preparations to incorporate [14-C] leucine was much reduced. Similar results were obtained in a study of [14-C] leucine incorporation in vivo in which rats were force-fed two meals and killed at various times after the last feeding. In rats fed the high tyrosine diet, incorporation of leucine into liver increased progressively; this was accompanied by a gradual decrease in leucine incorporation into muscle. In contrast, leucine incorporation into brain was immediately suppressed. In view of the apparently paradoxical effect of a high tyrosine load on protein synthesis in the liver, rates of the anabolic and catabolic phases of protein turnover in animals fed a high tyrosine diet were determined from radioactivity measurements made after pulse labeling them with [14-C] bicarbonate. Results indicated that the rates of both synthesis and degradation of liver proteins were elevated over control values. Differences in the effects of a toxic load of tyrosine on protein synthesis in the tissues examined could be the consequence of altered metabolic or hormonal balance as a result of nutritional stress.

Amino Acids↗
PubMedDate not supplied

Chemoprevention of mammary cancer with Se-allylselenocysteine and other selenoamino acids in the rat.

The present study examined the mammary cancer chemopreventive activity of Se-methylselenocysteine, Se-propylselenocysteine and Se-allylselenocysteine in the rat methylnitrosourea (MNU) model. Each compound was supplemented in the diet at a level of 2 ppm Se for the entire duration of the experiment after MNU dosing. Se-Allylselenocysteine was the most active and caused a reduction in total tumor yield by 86%. Se-Methylselenocyteine and Se-propylselenocysteine were similar but less effective, and both produced a decrease of about 50% in tumorigenesis. All three compounds were very well absorbed through the gastrointestinal tract. However, more selenium was excreted in urine after gavaging with Se-propylselenocysteine or Se-allylselenocysteine compared with Se-methylselenocysteine. Analysis of selenium in the mammary gland and other organs showed that tissue selenium levels did not appear to be correlated with differences in chemopreventive activity. A lyase activity capable of catalyzing scission of the Se-alkyl group from the remainder of the amino acid was demonstrated. This activity was found to be high in liver and kidney, but relatively low in mammary gland and intestine. Minimal variations in enzyme activity towards each of the substrates were observed. Our results support the concept that Se-alkylselenoamino acids could be used as precursors for delivering the Se-alkyl moiety and that intrinsic chemical differences in the Se-alkyl substituent of the test compounds are likely to be important determinants of their biological effects.

Animals↗