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M W Pariza

Publications and source records attributed to M W Pariza.

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

Calorie restriction, ad libitum feeding, and cancer.

The inhibition of cancer by calorie restriction was discovered over 50 years ago. By 1950 it had been well characterized and there existed sufficient data to propose a mechanism of action. For reasons that remain unclear, but are probably related to the perception of the calorie restricted rodent as "small" and the ad libitum feeding regimen as more "normal," the concept of calorie restriction has been largely ignored by investigators after this time. Hence, despite the fact that calorie restriction is one of the oldest, best-documented, and most effective ways known to reduce cancer risk in rodents, it has had little impact on modern cancer research. In this report the history of calorie restriction is briefly reviewed, and a mechanism of action is proposed that involves increased production of ACTH and decreased production of gonadotrophins. It is further proposed that these changes may come about in part from the restriction of the time during which feeding is permitted as well as from the restriction of food per se. There is renewed interest in calorie restriction due in part to the growing recognition that there are differences in the efficiency of utilization of various sources of energy, in particular that fat calories are utilized more efficiently and provide more usable energy than carbohydrate calories. New data are presented indicating that the apparent enhancement by dietary fat of mammary cancer in rats is really a manifestation of the caloric effect. Further, the effect is abolished by moderate calorie restriction of only 15-20%. The application of these findings to the prevention of cancer in humans is considered.

Adrenocorticotropic Hormone↗
PubMed1986

Net energy effects of dietary fat on chemically induced mammary carcinogenesis in F344 rats.

The effect of net energy, as distinct from kilocalorie intake or the percent of fat in the diet, on 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced mammary tumorigenesis in female inbred F344 rats was investigated. Rats were fed a 5% corn oil diet from weaning until DMBA administration, when they were switched to one of three dietary regimens: 5% corn oil diet, low-fat diet fed ad libitum (LF); 30% corn oil diet, high-fat diet fed ad libitum (HF); or 30% corn oil diet fed at a level providing a calculated net energy equivalent to the group on LF [high-fat diet fed at a restricted level (HF-R)]. Calculated relative net energy values of the amounts of diet actually consumed by the groups on HF-R, LF, and HF were, respectively, 0.90, 1.00, and 1.07 (kcal equivalent to 34.1, 42.2, and 40.8, respectively). Weight gain for the groups on LF and HF-R was the same throughout the experiment (24 wk), while rats on HF weighed significantly more at 6 weeks and thereafter. Body composition analyses at 24 weeks established that the groups on HF and HF-R were equivalent in fat: protein ratio, whereas the group on LF had about 35% less body fat and 15% more body protein. Carcass energy was in the following order for rats in these diet groups: HF greater than HF-R greater than LF. At 24 weeks, tumor incidences for the groups on HF, LF, and HF-R were, respectively, 73, 43, and 7%. These data indicated that tumor appearance does not depend on the percent fat in the diet per se but rather on a complex interaction involving energy intake, energy retention, and body size.

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

A beef-derived mutagenesis modulator inhibits initiation of mouse epidermal tumors by 7,12-dimethylbenz[a]anthracene.

Ground beef contains an organic solvent extractable mutagenesis modulator. Crude or partially-purified preparations of the activity were applied to the backs of SENCAR or CD-1 mice 5 min before application of 7,12-dimethylbenz[a]anthracene (DMBA). Controls received solvent (acetone) only prior to DMBA. Following 1-2 week intervals promotion was effected with twice-weekly applications of 12-O-tetradecanoylphorbol-13-acetate. Modulator-treated mice consistently developed fewer papillomas and exhibited lower tumor incidences than did positive control mice.

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

A perspective on diet, nutrition, and cancer.

This communication (1) reviews the controversy surrounding dietary recommendations aimed at reducing the incidence of cancer; (2) presents the somewhat conflicting conclusions of two National Research Council committees; (3) discusses a critique of these conclusions prepared by the Council on Agricultural Science and Technology; and (4) summarizes some of the epidemiologic data presented at a recent workshop conference sponsored by the American Cancer Society. The participants in the latter conference were divided on what advice the public should be given regarding diet, nutrition, and cancer. In a poll, two thirds of the participants indicated either that no advice was warranted or that general advice stressing the desirability of eating in moderation was adequate, based on current scientific knowledge.

Diet↗
PubMed1984

Effect of glutathione levels, sulfate levels, and metabolic inhibitors on covalent binding of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-acetylaminofluorene to cell macromolecules in primary monolayer cultures of adult rat hepatocytes.

The covalent binding of radiolabeled 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-acetylaminofluorene (AAF) to cell macromolecules was studied using primary monolayer cultures of adult rat hepatocytes. A time course for covalent binding was determined, and revealed similar levels of binding for both chemicals. Inhibition of glutathione synthesis by L-buthionine sulfoximine (1 mM) enhanced binding of both AAF and IQ with a greater increase observed for IQ. Addition of excess glutathione (10 mM) to the medium resulted in a slight decrease in IQ but not AAF binding. Addition of the P-450 inhibitor, 2-[2,4-dichloro-6-phenyl)-phenoxy]ethylamine (DPEA, 0.1 mM), resulted in almost total (94%) inhibition of IQ binding, with a lesser effect (42%) on AAF. Methimazole (1 mM), a competitive substrate of the flavin-containing monooxygenase, had no effect on the binding of either compound. Pentachlorophenol, an inhibitor of sulfate conjugation, decreased AAF binding substantially but produced a much smaller decrease in IQ binding. Addition of excess sulfate did not change the binding levels of either IQ or AAF. Cell density had little effect on IQ or AAF binding levels.

2-Acetylaminofluorene↗
PubMed1983

Activation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-aminofluorene for bacterial mutagenesis by primary monolayer cultures of adult rat hepatocytes.

Primary monolayer cultures of adult rat hepatocytes readily activate 2-amino-3-methylimidazo[ 4,5-f ]quinoline (IQ), a potent bacterial mutagen (Ames test) present in some cooked foods. In a co-culture system consisting of intact hepatocytes, bacteria, and IQ, the number of revertant colonies produced increased proportionately with hepatocyte density to a maximum at about 6 X 10(5) hepatocytes. When the density exceeded 6 X 10(5) hepatocytes per dish, the number of revertant colonies markedly declined. The decline was not due to bacterial death. In standard Ames tests disrupted hepatocytes prepared from similarly handled monolayer cultures or from hepatocytes just after isolation (uncultured), or rat-liver S9, were only about 1/10th as efficient as the co-cultured intact hepatocytes (at optimum density) in activating IQ for bacterial mutagenesis. In contrast, 2-aminofluorene was poorly activated by intact hepatocytes. Disrupted hepatocytes and rat-liver S9 in standard Ames tests were much more effective than co-cultured intact hepatocytes in activating 2-aminofluorene for bacterial mutagenesis. For intact hepatocytes an inhibitor of cytochrome P-450, 2-[(2,4-dichloro-6-phenyl)-phenoxyl]ethylamine, inhibited IQ activation by 94-98%, and AF activation by 64-70%.

Animals↗
PubMed1983

Inability of red beet betalain pigments to initiate or promote hepatocarcinogenesis.

A short-term bioassay was used to determine the ability of red-beet betalain pigments to initiate or promote hepatocarcinogenesis in rat liver. Female Sprague-Dawley rats were partially hepatectomized and separated into nine groups (6-11 animals/group). Four of the groups were treated with betacyanin pigment preparations (betacyanin solution after fermentation, 50 mg/kg; pure betanin, 50 mg/kg; degraded betanin, 50 mg/kg; a betacyanin diet containing 2000 ppm/kg) to evaluate their ability to initiate hepatocarcinogenesis. N-Nitrosodiethylamine (NDEA: 10 mg/kg) was used for the positive control. Another group, previously initiated with NDEA, received daily a betacyanin solution (100 ppm; 3.5 mg/rat/day) to determine the pigment's ability to promote NDEA hepatocarcinogenesis in comparison with positive and negative controls treated respectively with and without a promoting agent (0.5% phenobarbital in the diet). Animals were killed after month 6 (promotion test) or 8 (initiation test). Liver sections were stained with haematoxylin and eosin and for gamma-glutamyl transpeptidase (GGT) activity. The number of enzyme-altered foci and the percentage of liver volume so affected, were determined for each group, by scoring for GGT. Comparison of the results obtained for the experimental groups with those for positive and negative control groups indicated that the betacyanin pigments tested in this assay did not initiate or promote hepatocarcinogenesis in rat liver. These findings provide further evidence that betalain colourants may be viable alternatives for synthetic dyes currently used as food additives.

Animals↗
PubMed1983

Effects of carcinogens on hormonal regulation of gene expression in primary cultures of adult rat hepatocytes.

The report utilizes knowledge of the regulation of tyrosine aminotransferase (TAT) activity in rat liver as the basis for the development of a model system for investigating the effects of carcinogens on gene expression. A protocol utilizing primary monolayer cultures of adult rat hepatocytes was employed. The addition of dexamethasone resulted in a 5-fold induction of TAT activity; adding glucagon along with dexamethasone gave a 12-fold induction. The chemicals tested for possible effects on TAT induction were aflatoxins B1, B2, G1, G2, 2-acetylaminofluorene, 2-aminofluorene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzo[a]pyrene. Carcinogens inhibited the induction of TAT activity by dexamethasone alone or with glucagon in a dose dependent manner, and in general there was a correlation between inhibition of TAT induction and in vivo carcinogenic potency. In addition to the inhibition of TAT induction, the carcinogens similarly inhibited RNA synthesis and to a lesser extent, protein synthesis. The inhibition of these biochemical activities did not appear to be due to cell death.

Aflatoxin B1↗
PubMed1983

Mutagens and modulator of mutagenesis in fried ground beef.

It is now well documented that bacterial mutagens form in proteinaceous foods during cooking at moderate temperatures. Three heterocyclic amine mutagens have been identified by Sugimura and coworkers in fish and beef cooked under moderate heating conditions (T. Sugimura and S. Sato, Cancer Res. (Suppl.), 43: 2415s-2421s, 1983). The distribution of these known mutagens in commercial bacteriological-medium grade and food-grade beef extract, and in fried ground beef, is discussed. Of the known mutagens, we have been able to confirm only that 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline is present in fried ground beef. Deficiencies in currently used mutagen extraction procedures are addressed. It is likely that there are many mutagens in fried ground beef that are yet to be identified. Fried ground beef (and raw beef) also contains an activity which modulates bacterial mutagenesis apparently by interacting with rat liver microsomes which are added to metabolically activate promutagens. The modulator activity has been partially purified and either inhibits, enhances, or has no effect on promutagen activation depending on the promutagen under study and the pretreatment of the rat from which the microsomal fraction was obtained.

Animals↗
PubMed1982

Purification of two Clostridium perfringens enterotoxin-like proteins and their effects on membrane permeability in primary cultures of adult rat hepatocytes.

We isolated two proteins, ET-1 and ET-2, from the sporangial extracts of Clostridium perfringens type A. Both proteins had some properties in common with the well-known C. perfringens enterotoxin. ET-1 and ET-2 behaved as single and distinct entities in anion exchange chromatography and disk gel electrophoresis. ET-2 was the more anionic protein since it eluted more slowly from the anion exchange column and migrated faster toward the anode in polyacrylamide disk gel electrophoresis (pH 8.5, native gels). Additionally, in this electrophoretic system ET-2 was not distinguishable from the enterotoxin. The amino acid compositions of ET-1 and ET-2 were similar but differed in a few amino acid residues. The values for both proteins were also similar to the published reports of others for the enterotoxin. Both ET-1 and ET-2 showed lines of identity in agar gel double immunodiffusion against anti-enterotoxin antiserum. Both ET-1 and ET-2 were toxic for rat hepatocytes in primary monolayer culture as determined by accelerated exodus of L-[14C]glucose from preloaded cells and by the rapid uptake of 45Ca2+ after exposure to the proteins. In this regard, ET-1 and ET-2 appeared to be identical in mechanism of action to what has been regarded in the literature as "the" C. perfringens enterotoxin. Interestingly, ET-2 was 3 to 10 times more toxic on a weight basis than ET-1 was.

Amino Acids↗
PubMed1981

Activation of aflatoxin B1 by primary cultures of adult rat hepatocytes: effects of hepatocyte density.

Primary monolayer cultures of adult rat hepatocytes readily activate aflatoxin B1 as determined by bacterial mutagenesis (Ames test) and the extent of apparent covalent binding of aflatoxin B1 residues to hepatocyte macromolecules. For intact cultures inoculated with 3 X 10(5)-3 X 10(6) cells/dish, the efficiency of activation decreases with increasing cell density whereas permeabilized hepatocytes prepared from similarly-handled monolayer cultures show with increasing protein proportional increases in the capacity to activate aflatoxin B1. The density effect observed with intact cultured hepatocytes appears not to be due to substrate (aflatoxin B1) or oxygen depletion. These findings have apparent relevance to studies of carcinogen metabolism and in the design of carcinogen/mutagen testing protocols which utilize cultured hepatocytes.

Aflatoxin B1↗
PubMed1981

Enhancement of hepatic microsome-mediated bacterial mutagenesis by the rat liver soluble protein fraction.

Bacterial mutagenesis from aflatoxin B1, 2-aminofluorene and benzo[a]-pyrene, mediated by washed rat liver microsomes using the assay system of Ames, is elevated 2--4-fold by the liver soluble protein fraction. Enhancement results from an apparent stimulation of one (or possible more) biochemical steps leading to mutagenesis in this system. Enhancement is observed over a wide range of NADPH concentrations and is present in dialyzed preparations of liver soluble proteins. Enhancement activity is stable when the soluble protein fraction is stored for 18 h at pH 5-9 (4 degrees C); when stored for 18 h at 25 degrees C or 37 degrees C (pH 7.8), and when heated for 10 min at 56 degrees C. The activity is labile when heated for 10 min at 100 degrees C.

Aflatoxins↗
PubMed1981

Enhancement of N-hydroxy-2-aminofluorene bacterial mutagenicity by the soluble protein fraction from rat liver and partial purification of the enhancement activity.

Bacterial mutagenesis from 2-aminofluorene mediated by washed rat liver microsomes was elevated 2- to 3-fold by addition of the hepatic soluble protein fraction. Enhancement was observed at 2-aminofluorene concentrations between 1 and 20 micrograms/assay but not at 30 to 50 micrograms/assay. The soluble protein fraction (without added microsomes) did not activate 2-aminofluorene for bacterial mutagenesis. However, mutagenesis by N-hydroxy-2-aminofluorene or 2-nitrosofluorene was enhanced by the soluble protein fraction, but only when reduced nicotinamide adenine dinucleotide phosphate was also present. On the basis of chemical assay, reduced nicotinamide adenine dinucleotide phosphate reduced 2-nitrosofluorene to N-hydroxy-2-aminofluorene and protected the hydroxylamine from oxidation, thus indicating that it was the mutagenicity of N-hydroxy-2-aminofluorene (but not 2-nitrosofluorene) which was enhanced by the soluble protein fraction. Without the added soluble protein fraction, mutagenesis by N-hydroxy-2-aminofluorene or 2-nitrosofluorene was unaffected by reduced nicotinamide adenine dinucleotide phosphate. We succeeded in partially purifying a protein fraction with properties of the enhancement activity. The partially purified fraction, which represents a 14-fold increase in specific activity, was assigned a molecular weight of 33,500 by gel filtration through Sephadex G-100. This fraction was resolved into three components by polyacrylamide gel electrophoresis; the molecular weights of the three components were determined by sodium dodecyl sulfate-polyacrylamide gel (10%) electrophoresis to be 33,000, 27,000, and 16,250. The mechanism of mutagenesis enhancement remains unknown.

Animals↗
PubMed1980

Mechanism of action of Clostridium perfringens enterotoxin. Effects on membrane permeability and amino acid transport in primary cultures of adult rat hepatocytes.

Purified enterotoxin from the bacterium Clostridium perfringens rapidly decreased the hormonally induced uptake of alpha-aminoisobutyric acid in primary cultures of adult rat hepatocytes. At 5 min after toxin addition the decrease in alpha-aminoisobutyric acid uptake appeared not due to increased passive permeation (estimated with L-glucose) or to increased alpha-aminoisobutyric acid efflux. When short uptake assay times were employed a depression of alpha-aminoisobutyric acid influx was observed in toxin-treated hepatocytes. The depression of alpha-aminoisobutyric acid influx was correlated with a rapid increase in intracellular Na+ (estimated using 22Na+) apparently effected by membrane damage. In contrast, the uptake of cycloleucine in the presence of unlabeled alpha-aminoisobutyric acid (assay for Na+-independent amino acid uptake) by hepatocytes treated with toxin for 5 min was decreased to only a small extent or not at all depending upon experimental design. At later times, C. perfringens enterotoxin increased the exodus of L-glucose, 3-O-methylglucose and alpha-aminoisobutyric acid from pre-loaded cells indicating that the toxin effects progressive membrane damage. When enterotoxin was removed by repeated washing after 5--20 min the decay of alpha-aminoisobutyric acid uptake ceased and appeared to undergo recovery towards the hormonally induced control level. The degree of recovery of alpha-aminoisobutyric acid uptake was inverse to the length of time of exposure to toxin. Adding at 10 min specific rabbit antiserum against C. perfringens enterotoxin without medium change also reversed the effect of toxin on increased intracellular 22Na+, and on the exodus (from preloaded cells) of alpha-aminoisobutyric acid, L-glucose, and 3-O-methylglucose.

Amino Acids↗