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G J Hopkins

Publications and source records attributed to G J Hopkins.

34 records · Page 2Linked to original sources
PubMed1982

Comparison of different methods of isotopically labelling the esterified cholesterol in human high density lipoproteins.

Different methods of incorporating esterified [3H]cholesterol into human high density lipoproteins (HDL) have been assessed in terms of their influence on the subsequent rate at which esterified [3H]cholesterol was transferred from HDL to other plasma lipoproteins in 37 degrees C incubations containing tracer amounts of the labelled preparations added to aliquots of a common pool of unlabelled human plasma. Two basic methods were used to label the HDL esterified cholesterol: (a) by the action of lecithin: cholesterol acyltransferase in incubations of plasma containing exogenous [3H]cholesterol and (b) by exchange in incubations of plasma containing preparations of prelabelled LDL. The exchange labelling approach was also used to examine the effects of various HDL compositional changes on the subsequent behaviour of its esterified [3H]cholesterol. It was found that the source of the label, per se, whether from the esterification of exogenous [3H]cholesterol or from exchange with labeled LDL, had no influence on the subsequent behaviour of HDL esterified [3H]cholesterol. However, modification of the HDL composition during the labelling process had profound effects. For example, in preparations in which the esterified cholesterol content of the labelled HDL was increased by the action of lecithin: cholesterol acyltransferase, there was a reduced rate of transfer of esterified [3H]cholesterol out of the HDL fraction in subsequent incubations of the labelled HDL with fresh, unlabelled plasma. Conversely, when the esterified cholesterol content of the labelled HDL had been decreased by pre-incubation with Intralipid or very low density lipoproteins (VLDL), the subsequent rate of transfer of esterified [3H]cholesterol out of the HDL fraction was increased markedly. It has been concluded that to obtain a biologically valid, labelled tracer of human HDL esterified cholesterol, the labelling should be achieved with minimal modification to the HDL composition. This means labelling by exchange in incubations in which lecithin: cholesterol acyltransferase is inhibited in plasma from which VLDL has been removed.

Adolescent↗
PubMed1982

A unified model of esterified cholesterol exchanges between human plasma lipoproteins.

Exchanges of esterified cholesterol between human high density lipoproteins (HDL) and very low density lipoproteins (VLDL) and between VLDL and low density lipoproteins (LDL) have been fitted to a mathematical model previously developed to describe exchanges between human HDL and LDL. In all cases the fit of the model predicted exchanges to those measured experimentally was extremely good, thus greatly increasing confidence in the validity of the model. The model assumes that esterified cholesterol exchanges are achieved by means of a transfer protein which interacts with lipoprotein particles from which it picks up and deposits esterified cholesterol. The values generated for the model constants indicated that, given equal concentrations of esterified cholesterol in each fraction, the relative probability that the transfer protein will pick up a molecule of esterified cholesterol in HDL vs. VLDL vs. LDL is in the ratio 28.9:4.65:1. According to the model the transfer protein may 'bind' to lipoproteins. The model predicts that, at physiological lipoprotein concentrations, the proportion of transfer protein bound to HDL will be more than double that which is unbound to lipoprotein and that bound to VLDL will be about one tenth that unbound. The model was unable to detect evidence of the transfer protein binding to LDL.

Cholesterol Esters↗
PubMed1982

Dissociation of the in vitro transfers of esterified cholesterol and triglyceride between human lipoproteins.

This report describes the detailed time-course of in vitro net mass transfers of esterified cholesterol (EC) and triglyceride (TG) between human plasma lipoproteins incubated in the presence of EC and TG transfer proteins. In incubations containing high density lipoproteins (HDL), very low density lipoproteins (VLDL) and the thiol-group blocker parachloromercuriphenyl sulfonate (PCMPS) (which was added to inhibit EC production), the rate of EC transfer to VLDL was considerably more rapid than that of TG to HDL and equilibrium between the pools of EC was achieved much sooner than was the case for the pools of TG. When VLDL and low density lipoproteins (LDL) were incubated, the presence of PCMPS in the incubation mixture resulted in a marked reduction in the TG transfer to LDL, even though the EC transfer to VLDL was apparently unaffected. The molar ratio of the transfers of EC and TG was also examined in incubations of lipoproteins from a variety of human subjects. In incubations of HDL and VLDL (performed in the absence of PCMPS) there was a large individual variation (sixfold difference) in the molar ratio of the transfers of TG:EC. In incubations of LDL and VLDL from different subjects there was a twofold individual variation in the molar ratio of the transfers of TG:EC. It has been concluded that the net mass transfers of EC and TG between human lipoproteins do not involve a simple molecular exchange of one moiety for the other, as has been suggested previously, but are achieved by processes which are at least partially independent.

4-Chloromercuribenzenesulfonate↗
PubMed1981

Polyunsaturated fatty acids as promoters of mammary carcinogenesis induced in Sprague-Dawley rats by 7,12-dimethylbenz[a]anthracene.

The development of mammary tumors was examined in female noninbred Sprague-Dawley rats fed either a low-fat diet or high-fat diets containing different fats and fatty acid esters. Each rat was given 5 mg 7,12-dimethylbenz[a]anthracene by stomach tube 1 week before diets were introduced. Addition of 3% ethyl oleate (an ethyl ester of an unsaturated fatty acid) to a diet high in saturated fat (coconut oil) had no significant effect on tumor development, but the addition of 3% ethyl linoleate (an ethyl ester of a polyunsaturated fatty acid) increased the tumor yield to about twice that in rats fed either the high-saturated fat diet or a low-fat diet. Animals fed the high-saturated fat diet containing 3% ethyl linoleate developed as many tumors as those fed a 20% sunflower seed oil diet, though the sunflower seed oil diet contained about four times as much linoleate. Rats fed a high coconut oil diet containing 3% menhaden fish oil, which contains polyunsaturated fatty acids of the linolenate family (but having little linoleic acid), also developed as many tumors as those fed the 20% sunflower seed oil diet. These differences in mammary tumor yield could not be explained by alterations in the serum levels of prolactin, estrogen, or progesterone. However, the higher tumor yields were associated with increased unsaturation of mammary tissue phospholipids.

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

Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis.

High levels of dietary fat have been shown to promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene, and polyunsaturated fats were found to be more effective than saturated fats. In further studies it was found that diets containing 3% sunflowerseed oil (polyunsaturated fat) and 17% beef tallow or coconut oil (saturated fats) enhance tumorigenesis as much as a diet containing 20% sunflowerseed oil. Rats on these diets developed at least twice as many tumors as those fed diets containing either 3% sunflowerseed oil or 20% of the saturated fats alone. These results are in accord with human epidemiological data which show that breast cancer mortality in different countries is positively correlated with total fat intake but not with intake of polyunsaturated fat. Total fat intake varies greatly in different countries, but most human diets probably contain levels of polyunsaturated fat at least equivalent to 3% sunflowerseed oil.

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

Relationship between amount and type of dietary fat in promotion of mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.

Female Sprague-Dawley rats were fed semipurified diets containing various fats, either alone or in combination, to provide different amounts of dietary fat and linoleic acid. One week before commencing the diets, each rat received an intra-gastric dose of the carcinogen 7,12-dimethylbenz[a]anthracene. Rats fed diets containing mixtures of 3% sunflower seed oil and 17% of either tallow or coconut oil developed twice as many tumors as those fed 3% sunflower seed oil or 20% of either saturated fat alone. Tumor yields in the rats fed these mixed-fat diets were comparable to those in rats fed a 20% lard diet, which provided about the same amount of linoleic acid. No further increase in tumor yield was observed in rats fed a 20% sunflower seed oil diet that contained more than five times as much linoleic acid. These results show that a certain amount of polyunsaturated fat, as well as a high level of dietary fat, is required to promote mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in c3H-A vyfB mice: influence of different dietary fats.

The effect of a diet containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in C3H-A vyfB mice was examined. After receiving either diet for 28 days, some of the mice were given an intragastric dose of 5 mg DMBA. To identify the stage of carcinogenesis that might be influenced by dietary fat, the diets of half of the mice were then interchanged so that those previously fed the saturated fat diet were fed the polyunsaturated fat diet and vice versa. The cumulative incidence of tumor-bearing mice was significantly greater among the females fed the polyunsaturated fat diet compared to those fed the saturated fat diet. This enhancement of carcinogenesis was observed only when the mice were fed the polyunsaturated fat diet after DMBA administration. Similar trends were observed in the male mice, but these mice developed fewer tumors and none of the differences between the tumor incidences were statistically significant. The most common sites for tumors in the male mice were the liver, lungs, and skin, whereas those for tumors in the females were the mammary glands and ovaries. The differences in tumor incidence suggest that carcinogenesis was enhanced by the polyunsaturated fat diet during the promotion stage of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Diet-induced changes in the fatty acid composition of mouse hepatocyte plasma membranes.

Hepatocyte plasma membranes were isolated from the livers of mice fed either a low fat diet or high fat diets containing polyunsaturated or saturated fat. The combined rate and isopycnic ultracentrifugation technique which was used produced highly purified hepatocyte plasma membrane fractions. The efficacy of the procedure was checked by electron microscopy and the assay to marker enzymes for the different subcellular organelles. Mice were maintained on a low fat diet until 60-70 days of age, when they were fed high fat diets containing polyunsaturated fat. The hepatocyte plasma membrane lipids of mice fed the polyunsaturated fat diet for 4 wk contained increased proportions of the major dietary unsaturated fatty acid, linoleic acid, and increased proportions of arachidonic acid. The proportion of linoleic and arachidonic acids decreased with continued feeding of the polyunsaturated fat diet. The hepatocyte plasma membrane lipids of mice fed the saturated fat diet contained increased proportions of oleic acid.

Animals↗
PubMed1977

Effect of dietary polyunsaturated fat on the growth of a transplantable adenocarcinoma in C3HAvyfB mice.

Weaning male and female C3HAvyfB mice were fed a low-fat (4.5%) diet until they were 60-70 days of age when they were fed high-fat (18.6%) diets containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet). After receiving either of the high-fat diets for 4 weeks, each mouse received an inoculum of approximately 1,700 single cells from a transplantable mammary adenocarcinoma. The cumulative incidence of tumor-bearing mice was significantly greater among both males and females fed the polyunsaturated fat diet than among males and females fed the saturated fat diet. The mean times elapsed before palpable tumors developed were less when mice were fed the polyunsaturated fat diet than when mice were fed the saturated fat diet, but these differences were not statistically significant. The cumulative incidence of tumor-bearing mice was also significantly greater among females than males. The results supported the suggestion from previous work in this laboratory that the polyunsaturated fat diet exerts its effect on the promotional stage of carcinogenesis rather than on the initial event of neoplastic transformation.

Adenocarcinoma↗
PubMed1976

Effect of dietary fats on pentobarbitone-induced sleeping times and hepatic microsomal cytochrome P-450 in rats.

Female Wistar-derived rats were fed diets containing either sunflowerseed oil or tallow for 4 weeks. Rats fed the sunflowerseed oil diet had longer pentobarbitone-induced sleeping times and lower concentrations of hepatic microsomal cytochrome P-450 than rats fed the tallow diet. The addition of pentobarbitone to the drinking water of rats caused approximately 2-fold increases in the concentrations of hepatic microsomal cytochrome P-450 but did not alter the relative effect of the diets.

Animals↗
PubMed1976

Effect of dietary fats on the incidence of 7,12-dimethylbenz(a)-anthracene-induced tumors in rats.

Female rats have been fed high fat diets containing either polyunsaturated or saturated fat. After being fed either of the diets for 4 weeks, some of the animals received an intragastric dose of 7,12-dimethylbenz(a)anthracene (DMBA). At this point, the diets of half of the animals were interchanged so that animals previously fed the polyunsaturated fat diet were fed the saturated fat diet and vice versa. The cumulative incidence of tumor-bearing rats among DMBA-dosed rats was greater when the polyunsaturated fat diet was fed. The mean induction time of tumors decreased and the proportion of tumor-bearing rats which developed malignant tumors increased when the polyunsaturated fat diet was fed. This promotional effect of the polyunsaturated fat diet was exerted only when the diet was fed after DMBA administration.

9,10-Dimethyl-1,2-benzanthracene↗