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R R Dils

Publications and source records attributed to R R Dils.

28 records · Page 2Linked to original sources

Transport and cellular uptake of polychlorinated biphenyls (PCBs)--II. Changes in vivo in plasma lipoproteins and proteins of pigeons in response to PCBs, and a proposed model for the transport and cellular uptake of PCBs.

The complex distribution of polychlorinated biphenyl (PCB) isomers and congeners amongst plasma fractions of the pigeon suggests that the lipid and apolipoprotein components of lipoproteins, as well as plasma proteins, may be important in transporting PCBs to tissues (Borlakoglu et al., Biochem. Pharmac. 40, 265 (1990]. Pigeons were injected with the commercial PCB mixture Aroclor 1254 (1.5 mmol/kg body weight). After 120 hr triacylglycerol-like droplets accumulated in hepatocytes ('fatty liver syndrome'), there was proliferation of the hepatic smooth endoplasmic reticulum, and plasma concentrations of triacylglycerol and total cholesterol increased. This was accompanied by significant decreases in plasma concentrations of total protein, total apolipoproteins of the low density lipoprotein (LDL) and the high density lipoprotein (HDL) fractions, and albumin and by a significant increase in that of urea, indicating increased protein breakdown. These results suggest that Aroclor 1254 increased hepatic lipid synthesis, but decreased hepatic production of albumin and apolipoproteins. This would explain the accumulation of triacylglycerol in the liver and the increase in the proportion of triacylglycerol to apolipoprotein in the total lipoproteins. From the evidence presented, a model is proposed based on the association of PCBs with hydrophobic domains of lipids and proteins for the transport of PCBs by plasma fractions, their uptake into cells and intracellular metabolism, and their accumulation in adipose tissue.

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Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers.

1. Polychlorinated biphenyls (PCB) are abundant and persistent pollutants in the ecosystem. Commercial mixtures (e.g. Aroclor 1254) can contain up to 80 different isomers and congeners, many of which accumulate in biological systems by the ingestion of PCB-contaminated lipid components of food chains. 2. Commercial mixtures of PCB induce, in hepatic microsomal membranes in vivo, a variety of different forms of the cytochrome P-450 components of enzyme systems involved in the metabolism of drugs and other xenobiotics, and can also induce the proliferation of this membrane. Since these microsomal enzyme systems share a number of the requirements of microsomal fatty acid desaturases, we have investigated whether the induction by PCB in vivo of cytochrome-P-450-linked enzymes in the proliferating hepatic microsomal membrane of the pigeon and the rat is accompanied by increased proportions of polyunsaturated fatty acids in this membrane. 3. The most striking changes observed 120 h after treating pigeons and rats with 1.5 mmol Aroclor 1254/kg body mass were 2.2-fold and 1.6-fold increases, respectively, in the proportion of arachidonic acid in the hepatic microsomal membrane. When the effects of this treatment on the proliferation of this membrane and increase in liver mass are taken into account, the amount of arachidonic acid in the total microsomal membrane of pigeon and rat livers increased 6.7-fold and 1.9-fold, respectively. 4. These changes were accompanied by very significant increases in pigeons and rats of the concentration of hepatic microsomal cytochrome P-450, and in the activity in microsomal protein of a wide range of cytochrome P-450-dependent enzyme involved in the metabolism of drugs and other xenobiotics. 5. This effect of PCB, of increasing in vivo the degree of unsaturation of fatty acids of hepatic microsomal membrane, appears to be a novel finding, and does not seem to have been investigated for other drugs and xenobiotics. Preliminary results have shown that the effect is accompanied by substantial increases in the total activity of delta 6 and delta 5 microsomal fatty acid desaturases converting 18:2 (9, 12) (linoleic acid) to 20:4 (5, 8, 11, 14) (arachidonic acid) [Borlakoglu, J.T., Dils, R.R., Edwards-Webb, J.D. & Walker, C.H. (1988) Biochem. Soc. Trans. 16, 1072]. 6. It is postulated that there is a significant link between increased fatty acid desaturation and the induction of cytochrome-P-450-linked enzymes, and this is discussed in terms of the mechanisms involved in the metabolism of foreign compounds.

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Evidence for the induction of cytochrome P-452 in rat liver by Aroclor 1254, a commercial mixture of polychlorinated biphenyls.

We have examined the ability of a commercial mixture of polychlorinated biphenyls (Aroclor 1254) to induce hepatic cytochrome P-452-linked enzyme activities in rat and pigeon liver five days after its intraperitoneal injection. The results provide evidence that, at the doses used, Aroclor 1254 induces cytochrome P-452-linked enzyme activities in rats, but not in pigeons. This inductive effect was previously regarded as being specific for hypolipidemic drugs and phthalate ester plasticisers.

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Comparative aspects of milk fat synthesis.

This general review attempts to capture the interest of nonspecialists, especially those whose main interest is the dairy cow, in the extraordinary diversity of milk fats synthesized and secreted by different mammalian species. The review compares differences in the gross proportions of fats in the milk of various species and discusses different strategies for providing the suckling young with sufficient energy as fat. Despite the constancy of the gross chemical composition of the milk fat globule and its membrane produced by mammals, there are striking differences among species in the fatty acid composition of milk triacylglycerols (triglycerides). The origins of the short-, medium-, and long-chain fatty acids of milk triacylglycerols are reviewed with emphasis on differences between ruminants and nonruminants. Because there appears to be less difference among mammals in the mechanisms of fatty acid desaturation, chain elongation, and esterification by the mammary gland, these topics are only briefly reviewed.

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Novel multialveolar epithelial structures from rabbit mammary gland that synthesize milk specific fatty acids in response to prolactin.

Multialveolar mammary epithelial structures have been prepared from rabbit mammary gland by treating the tissue with collagenase plus hyaluronidase. These structures synthesize milk specific fatty acids when cultured with physiological concentrations (0.5 micrograms/ml) of prolactin in the presence of insulin and corticosterone. They have many of the advantages but few of the disadvantages of either mammary explants or primary cells in culture. For example, they are easily prepared in large numbers and respond to prolactin in culture even in the absence of serum or other tissue extracts. Because their level of organization is intermediate between that of explants and single cells, they provide a complementary system for studies on mammary differentiation.

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