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M W Pariza

Publications and source records attributed to M W Pariza.

At least 55 records · Page 3Linked to original sources
PubMed1992

A new approach to evaluating carcinogenic risk.

Carcinogenic risk assessments are based on extrapolating from high-dose chronic rodent-feeding studies to human-exposure levels. A serious problem is that about half of all substances tested at their respective maximum tolerated dose (MTD) are found to induce cancer. The MTD as currently defined has been criticized because it may stimulate cell proliferation in susceptible tissues. Such chemically induced mitogenesis is postulated to increase the probability that neoplasia will develop at the affected site. It is proposed that, in the development of an MTD for a given substance, chemically induced mitogenesis be considered an undesirable toxic manifestation. Hence, mitogenesis should not be induced by a substance fed at its true MTD. Since MTDs determined in this fashion are likely to be lower than those developed using current criteria, an added level of protection is introduced by employing a safety factor similar to that used now in determining acceptable daily intakes for noncarcinogenic food additives. In calculating acceptable daily intakes, the usual safety factor is 100; i.e., the acceptable daily intake is set at 1% of the no-observed-effect level. Hence it is proposed that the acceptable daily level of exposure to a substance that does not induce cancer at its MTD as defined herein be set at 1% of that MTD. On the other hand, a chemical that induces cancer at its MTD as defined herein would continue to be regulated as is customary now.

Animals↗
PubMed1992

Risk assessment.

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Animals↗
PubMed1992

Designer foods: effects on development of cancer.

There are numerous anticarcinogens in the diet. An important question is how to use such substances in an effective, directed way to reduce cancer risk in humans. The "designer foods" concept is one approach for accomplishing this goal. Foods would be engineered to contain effective levels of anticarcinogens. This idea will work only to the extent that there is sufficient scientific knowledge on which to base such food design. Obviously, it is not sufficient simply to extrapolate from animal data to humans. A hypothetical example of the possible "designer fat substitute" is presented and discussed.

Diet, Reducing↗
PubMed1991

Mammary cancer prevention by conjugated dienoic derivative of linoleic acid.

Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose-dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by dietary soy sauce.

We show that Japanese-style fermented soy sauce (shoyu) contains anticarcinogenic activity. Female ICR mice were fed a semipurified diet containing soy sauce (0-30%). Two weeks later a regimen consisting of 4 doses of benzo(a)pyrene (1 dose/week p.o. for 4 weeks) was begun to initiate forestomach neoplasia. Twenty-three weeks after the first intubation the animals were sacrificed, and forestomach neoplasms were counted and histologically confirmed. Soy sauce produced a significant dose-dependent reduction in forestomach neoplasms, which appeared to be maximal when soy sauce constituted 20% of the diet. Exposure to nitrite (0-500 ppm through drinking water) neither enhanced nor diminished the anticarcinogenic effect of the dietary soy sauce. Soy sauce was found to contain antioxidant activity which may be related to the observed anticarcinogenic effect. Contrary to expectations, mouse forestomach ornithine decarboxylase activity was induced by soy sauce. This appeared to be due at least in part to the relatively high sodium chloride content of soy sauce.

Animals↗
PubMed1991

Formation and action of anticarcinogenic fatty acids.

Conjugated dienoic derivatives of linoleic acid (referred to by the acronym CLA) constitute a newly recognized class of anticarcinogenic fatty acids. Of the eight major CLA isomers, the cis-9, trans-11 isomer alone is incorporated into phospholipid and may be the most biologically relevant isomer. CLA exhibits potent antioxidant activity; evidence is presented indicating that CLA acts both as an in vitro and in vivo antioxidant. The formation of CLA in foods, and its possible biological significance in cell membranes, is discussed.

Animals↗
PubMed1990

Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid.

Grilled ground beef contains factors that inhibit the initiation of mouse epidermal carcinogenesis by 7,12-dimethylbenz(a)anthracene. Previously we isolated an active principal and characterized it as an isomeric mixture of conjugated dienoic derivatives of linoleic acid (CLA). We now show that synthetic CLA inhibits the initiation of mouse forestomach tumorigenesis by benzo(a)pyrene. Four and 2 days prior to p.o. treatment with benzo(a)pyrene, female ICR mice were given (a) CLA in olive oil, (b) linoleic acid in olive oil, or (c) olive oil alone or plus 0.85% saline (control groups). Three days later the cycle was repeated for a total of 4 times. At 30 wk of age, the mice were sacrificed. In three independent experiments, mice treated with CLA developed only about half as many neoplasms/animal as mice in the control groups (P less than 0.025); in two of the experiments tumor incidence was also reduced (P less than 0.05). There were no significant differences in food intake or body weight among the groups. High-performance liquid chromatography/gas chromatography analysis established that, following intubation, only the c-9, t-11 CLA isomer was incorporated into forestomach phospholipids. In studies aimed at elucidating the mechanism of action, we found that CLA is an effective antioxidant. Under the conditions of the test CLA was more potent than alpha-tocopherol and almost as effective as butylated hydroxytoluene. These observations indicate that CLA might serve as an in situ defense mechanism against membrane attack by free radicals and may, at least in part, explain the anticarcinogenic properties of CLA.

Animals↗
PubMed1990

Newly recognized anticarcinogenic fatty acids.

Evidence leading to the recognition of the anticarcinogenic activity of the conjugated dienoic derivatives of linoleic acid (CLA) is reviewed. New data indicate that CLA has potent antioxidant activity. Because the c-9, t-11 CLA isomer is esterified in phospholipid, it may represent a heretofore unrecognized in situ defense mechanism against membrane attack by oxygen radicals.

Animals↗
PubMed1990

Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens.

Evidence establishing the anticarcinogenic activity of the conjugated dienoic derivatives of linoleic acid (CLA) is reviewed. Our findings demonstrate that CLA is a potent antioxidant and that the c-9,t-11 CLA isomer is selectively incorporated into cellular phospholipid, which may at least in part explain the anticarcinogenic activity of CLA. Dietary sources of CLA include grilled beef, cheese, and related foods. Another source of CLA is its endogenous generation via the carbon centered free radical oxidation of linoleic acid. We propose that the formation and action of CLA represents a previously unrecognized in situ defense mechanism against membrane attack by oxygen radicals.

Animals↗
PubMed1988

Reduction of benzo[a]pyrene-induced forestomach neoplasms in mice given nitrite and dietary soy sauce.

This study was conducted to determine the effects of nitrite (0.05% in drinking-water) and soy sauce (20% in a refined diet) on the initiation and promotion of benzo[a]pyrene-induced forestomach neoplasia in ICR mice. In two experiments nitrite and soy sauce together significantly reduced the number of neoplasms per animal. Soy sauce (without nitrite) produced a smaller apparent (non-significant) reduction whereas nitrite (without soy sauce) had no effect. Evidence suggested that soy sauce might contain factors that reduce calorie absorption or utilization, but this observation was independent of the inclusion of nitrite in the drinking-water and therefore could not by itself explain the significant reduction in neoplasms in mice given soy sauce plus nitrite. Protection appeared to primarily involve the tumour promotion stage.

Animals↗
PubMed1987

Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid.

Fried ground beef contains substances that inhibit mutagenesis in bacteria and the initiation of epidermal carcinogenesis in mice by 7,12-dimethylbenz [a]anthracene (DMBA). The inhibitors apparently act at least in part via inhibition of cytochrome P-450 activity. A highly purified fraction that inhibited cytochrome P-450 activity in vitro was isolated by HPLC and characterized by GC-MS, and by UV and proton NMR spectroscopy. The fraction contained four isomeric derivatives of linoleic acid each containing a conjugated double-bond system (designated CLA). Synthetically prepared CLA (containing all four isomers) was tested for anti-initiation activity in the two-stage mouse epidermal carcinogenesis system. Seven days, 3 days and 5 min prior to DMBA application, CLA was applied at doses of 20, 20 and 10 mg respectively. Control mice were treated similarly with linoleic acid or solvent (acetone). One week after initiation, and twice weekly thereafter, all mice were treated with 12-O-tetradecanoylphorbol-13-acetate to effect tumor promotion. There was no difference in tumor incidence or yield between linoleic acid-treated mice and solvent-treated control mice. By contrast, the CLA-treated mice developed only about half as many papillomas and exhibited a lower tumor incidence compared with the control mice.

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

Dietary fat and neoplasia--the role of net energy in enhancement of carcinogenesis: effects of fat and calories on the immune system.

The mechanism by which carcinogenesis is enhanced by dietary fat is not understood. We know that a minimum level of essential fatty acids (EFA) is necessary for mammary tumor development and that this level probably exceeds the normal requirements of rats. Once the minimum level of EFA has been supplied, the calorie contribution of dietary fat may account for its enhancement of carcinogenesis. In this regard, we must recognize that the efficiency with which dietary energy is utilized is known to increase as the fat content of the diet is raised. Hence even when fed isocalorically to low fat diets, high fat diets will provide more net energy. Modulation of host immunity has been proposed as a mechanism of action of both fat and calorie intake on neoplasia. We review the literature examining the effects of fat and calories on the cell-mediated immune system, that arm of the immune system most directly responsible for the killing of neoplastic cells.

Dietary Fats↗
PubMed1986

Modulation of carcinogenesis by dietary factors.

The purpose of this report is to present recent data on two modulating factors of carcinogenesis that are found in Western-type diets: a beef-derived mutagenesis modulator that has been shown to inhibit the initiation of epidermal carcinogenesis in mice, and the possible role of net energy rather than dietary fat per se in the enhancement of rat mammary carcinogenesis.

Animals↗