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Nutrient Interactions and Toxicity

Total Equivalent of Reactive Chemicals in 142 Human Food Items Is Highly Variable Within and Between Major Food Groups¹

Min He^*, Kyle Openo, Marji McCullough^** and Dean P. Jones^*,,2

^* Nutrition and Health Sciences Program, Division of Biological and Biomedical Sciences, and Department of Medicine and Clinical and Molecular Nutrition Center, Emory University, Atlanta, GA 30322; and ^** Epidemiology and Surveillance Research Department, American Cancer Society, Atlanta, GA 30329

²To whom correspondence should be addressed. E-mail: dpjones{at}emory.edu.

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Many reactive electrophilic chemicals (e.g., acrylamide and hydrazine) occur in foods, and these could individually or cumulatively contribute to human cancer or other diseases. Glutathione (GSH) reacts with and detoxifies electrophilic compounds and is used physiologically to protect against a broad range of toxic and mutagenic compounds. To elucidate the distribution of reactive chemicals in foods, we added a known amount of GSH to 142 commonly consumed food items and assayed the relative amounts of reactive chemicals in terms of the amount of GSH lost during homogenization and extraction, defined quantitatively in terms of glutathione-reactive units (GRUs). Thirty-four items contained GRUs but no detectable GSH; 53 items contained both GSH and GRUs; 18 items contained no GSH or GRUs; and 37 items contained GSH but no detectable GRUs. Among the food groups, cereals, bread, milk, and milk products had relatively high GRU concentrations and low GSH concentrations; several common beverages also had high GRU concentrations and low GSH concentrations; meats and main course dishes were generally low in GRUs and high in GSH. Fruits and vegetables varied in GRU concentration, but most fresh fruits and vegetables had considerably more GSH than GRUs; exceptions were canned vegetables, which had no GSH or GRUs; fruit drinks, which had moderate levels of GRUs and no GSH; and 3 fruits (blueberries, cherries, and prunes), which had high GRU levels. The results provide a database that can be used with food frequency analyses to evaluate the possible association of health risks with the consumption of foods high in GSH-reactive chemicals.

KEY WORDS: • toxicology • food composition • glutathione • electrophile • chemoprevention

Public health regulations and recommendations are based in part on strategies to minimize the presence of carcinogenic chemicals in the food supply. Nonetheless, low levels of known carcinogenic chemicals are present in food items (1). In principle, these reactive chemicals could contribute not only to cancer but also to a range of toxicities, including teratogenesis and birth defects, renal failure, vascular disease, and autoimmune diseases. The majority of carcinogens found in foods undergo biological activation in vivo, but there are also direct-acting carcinogens, which have an inherent reactivity with nucleophilic sites in DNA (2). Attention has recently focused on one of these, acrylamide, which is present at unexpectedly high levels in certain fried foods (3). Acrylamide is formed from the breakdown products of PUFAs and amino acids or proteins (4,5) and is carcinogenic in animal studies (6–9). However, the hazard from dietary exposure is uncertain because of the likelihood that most, if not all, of the amounts observed in foods are detoxified prior to reaching vulnerable sites in cells.

Factors affecting bioavailability include central mechanisms that protect against reactive electrophiles by conjugation with the small cysteine-containing peptide, glutathione (GSH)³ (2). The first line of defense against direct-acting carcinogens is found in the gastrointestinal tract, where detoxification by GSH is enhanced by glutathione S-transferases (2). Glutathione S-transferase activity is present in the mucus lining the intestinal epithelium, and this activity uses GSH from the bile and dietary sources to detoxify electrophiles prior to absorption (10). Conjugation also occurs within the epithelial cells lining the GI tract. These cells synthesize GSH and also have transport mechanisms the allow GSH to be utilized directly from the lumen (11). Studies with isolated rat enterocytes indicate that up to 80% of the GSH supply in the small intestinal enterocytes can be derived from transport, that is, from hepatic GSH released into the lumen in bile or from dietary sources (12). These multiple lines of defense decrease the bioavailability of reactive chemicals and minimize health risks from dietary intake of reactive chemicals. However, one can expect that risk would increase with an imbalance between the detoxification capability and the amount and reactive character of the electrophiles in foods.

We previously measured the GSH concentration of foods in the National Cancer Institute’s Health Habits and History Questionnaire (HHHQ) to provide a database to evaluate whether dietary GSH intake was associated with a reduced risk of cancer (13). Analysis of the association between dietary GSH intake and risk of oral and pharyngeal cancer (14) in a population-based, case-control study showed that the relative risk of cancer was 0.5 among people with the highest quartile of GSH intake (95% CI = 0.3–0.7). However, only GSH from fruit and from vegetables commonly consumed raw (carrots, fresh tomatoes, cole slaw, lettuce, cucumbers, and green peppers) was associated with reduced risk of oral cancer (14). The results implied that some additional factors in foods, such as chemicals that react with GSH, could determine the beneficial effect of dietary GSH. Such chemicals could alter GSH bioavailability and therefore modulate a beneficial effect. Alternatively, isothiocyanates, which can induce GSH synthesis, could be transported by forming a reversible adduct with GSH (15) and provide enhanced protection both by delivering GSH and by increasing GSH synthesis.

The present study was designed to determine which foods contain GSH-reactive chemicals and to provide a database so that possible associations between levels of reactive chemicals in the diet and health risks, including specific types of cancer, could be examined. A comprehensive analysis of individual reactive electrophiles in foods was considered to be unwieldy, but an operational measure of total reactive chemical concentration was considered feasible if done in terms of the amount of GSH lost when a known amount of GSH was added. Consequently, we determined the GSH concentration remaining after timed homogenization of foods in solutions containing a known concentration of GSH. The amount of GSH lost provided a quantitative measure of the total equivalent of reactive chemicals, expressed as GSH-reactive units (GRUs).

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Materials. Dithiothreitol, 1-fluoro-2,4-dinitrobenzene (FDNB), ethylenediamine tetraacetic acid, GSH, -glutamylglutamate, iodoacetic acid and dansyl chloride were purchased from Sigma Chemical. All other chemicals were at least of reagent grade and purchased locally.

    Selection of representative foods. Foods were selected from items on the food frequency portion of the HHHQ as previously described (13). To capture the possible range of variation for each food item, 3 different brand names or samples from 3 different markets or food establishments were used. Perishable foods from groceries and markets were refrigerated until laboratory analysis, which was performed within 1 wk of purchase. Prepared foods from restaurants, delicatessens, and the like were analyzed immediately upon return to the laboratory.

    Sample preparation. The samples were taken from the portions of the foods generally considered edible in the United States and prepared as previously described (13). Briefly, a 1-g sample was placed in a beaker, and 10 mL of 0.9 g/L NaCl solution containing 1 mmol/L EDTA or the same solution containing 20 µmol/L GSH was added. Samples were homogenized for 2 min in a Polytron homogenizer. For each set of analyses, blanks with 1 mL of distilled, deionized water were tested to assay the recovery of GSH from the homogenization solution alone (i.e., without added food). Foods consisting of solutions or homogenates were mixed on a vortex shaker for 2 min. A 1-mL aliquot was then added to a test tube containing 0.5 mL of ice-cold 300 g/L trichloroacetic acid. Samples were centrifuged to remove insoluble material prior to derivatization and analysis by HPLC (16). Parallel analyses with 1 mmol/L dithiothreitol were performed on all samples to assay the amount of GSH that was lost by oxidation rather than by irreversible reaction with electrophiles. A small number of items (skim milk, 2% milk, biscuit, and pork sausage) were analyzed using a modification of this method (17), with dansyl chloride rather than FDNB and detection by fluorescence. This modification is comparable to the original method but has greater sensitivity (17).

    Expression of data and statistics. The GRU level was calculated as the sum of values for food alone (homogenized in saline) and the solution containing GSH alone, minus the value for food homogenized in solution containing GSH, i.e., (integral for GSH recovered/g food + integral for 20 µmol/L GSH) – (integral for food homogenized in the presence of 20 µmol/L GSH). In each case, an appropriate factor (11/1 or 11/10, respectively) was included to correct for dilution (1 g of sample + 10 mL of solution). Descriptive statistics include the mean GRU concentration ± SD (nmol/g), given for each food item in the supplemental data.⁴ The CV of the HPLC method was 5%; thus, the large SD values for some food items were due to large differences between samples for those items, not to experimental error. These were not further studied but indicate that variation is likely among different samples of these foods. To facilitate comparison in terms of human meals, values were converted to nmol per usual portion using the HHHQ medium portion sizes from the National Cancer Institute’s Health Habits and History database (18,19). Listed GSH concentration values were converted from published values (13) using the molecular weight of GSH (307 g/mol).

	RESULTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
The data for GRU concentration (nmol/g wet wt; see supplemental data) show considerable variation among food items (Fig. 1). Although only small numbers of items were analyzed among 12 common food groups, the results were sufficient to conclude that alcoholic beverages, nonalcoholic beverages, condiments, dairy products, fats, fruits, grains, meats, mixed dishes, other protein sources, snacks and sweets, and vegetables all included foods with a range of GRU concentrations. Because different food items varied considerably in portion size, this information was recalculated according to portion size and, to facilitate comparison in terms of possible health risks and benefits, ranked according to net GRU content (Tables 1, 2, 3, 4).

View larger version (15K): [in this window] [in a new window]   FIGURE 1 Highly variable concentrations of GSH-reactive chemicals in foods within food groups. (Upper panel) Data for the loss of GSH (nmol/g wet wt) during extraction under standardized conditions, expressed as GRU, are summarized for each of the 12 food groups listed in the supplemental data. Each data point shows the absolute GRU value for an individual food item, which is the mean of 3 samples for each item, each measured in triplicate. (Lower panel) Net concentration of GSH-reactive chemicals, after subtraction of GSH in foods, grouped according to food group. The GSH concentration (nmol/g wet wt) listed in the supplemental data was subtracted from the amount of GSH (nmol/g wet wt) lost during extraction (GRU) to obtain the net GRU value for each of the 12 food groups. Each data point shows the net GRU value for an individual food item. Negative values indicate that the GSH concentration was greater than the GRU concentration.

Among dairy products, all items except yogurt contained GRUs but no GSH. Yogurt had no GRUs or GSH. Samples of milk containing various percentages of fat did not differ in net GRU content, indicating that the rather high GRU concentration of whole milk was not simply related to fat content. Among high-fat items, all had rather high GRU content and no GSH.

Most of the fruit items contained GRUs, but most also contained GSH; thus, the net GRU content was generally negative. Blueberries, cherries and dried prunes were the only items with high GRU content and no GSH. Canned and bottled fruit juices were similar to other nonalcoholic beverages in that they had moderate GRU concentrations and no GSH. Canned fruit typically contained no GRUs or GSH. In contrast, essentially all of the fresh fruits contained GSH at concentrations considerably higher than those of GRU.

Grain products largely fell into 2 groups. All corn products and enriched white bread contained GRUs and little to no GSH. In contrast, oatmeal, rice, and whole wheat bread had relatively high GSH levels and low GRU levels. Bran flakes had nearly equivalent concentrations of GRUs and GSH.

Among the meat products, most had very low GRU levels, and many had very high GSH levels. The meats with the highest GRU concentrations were hamburger, frankfurters, boiled ham, and bacon. In contrast, main dish items (listed among mixed dishes) generally had low GRU levels, but most also had low GSH levels. Other protein-containing items, including eggs, peanut butter, and tofu, contained no GRUs.

Several sweets and snack foods were analyzed. Most of these had low GRU and GSH levels.

Vegetables varied in concentration of both GRUs and GSH. In general, canned vegetables contained no GRUs or GSH. Most of the raw and cooked fresh vegetables had low to moderate GRU concentrations and considerably higher GSH concentrations. Thus, in general, fresh vegetables were comparable to fresh fruits in having low (highly negative) net GRU levels.

Food items containing GRUs but no detectable GSH were listed together (Table 1). To facilitate comparison in terms of human intake, GRU concentration values were multiplied by the mean portion size to give an estimate of GRU intake per serving, then ranked according to GRU intake per serving. Nine food groups were included in this list, indicating that GRU content in the absence of GSH occurs broadly among different types of food. Ranking by intake per portion provided a simple way to compare GRU intake and emphasized the conclusion that total intake is likely more important than concentration. For instance, sweet cherries supplied the highest GRU/g concentration, but milk supplied the highest GRU intake per average portion. As indicated above, most of the items in the beverage, condiment, dairy, and fat groups contained GRUs but no GSH; 24% of all fruit items but only 6.7% of all vegetable items contained GRUs but no GSH. The rankings by intake per portion showed that some items often consumed in multiple servings per day contained relatively high net GRU levels. These included milk, tea, coffee, and enriched white bread. Similar items consumed in multiple servings by some individuals included prunes, blueberries, apple juice, and American cheese.

Many foods from various food groups contained both GSH and GRUs (Table 2), whereas some foods contained only GSH and no detectable GRUs (Table 3). The values used were net GRU per medium portion. Negative numbers indicated that GSH content was greater than GRU content. The 53 food items with both GSH and GRUs (Table 2) were from 7 food groups and included most fruits, meats, and vegetables: 40% of the fruit items, 39% of the meat items, and 51% of the vegetable items. The 37 items that contained GSH but no GRUs (Table 3) included 28% of the fruit items, 61% of the meat items, and 33% of the vegetable items listed in the supplemental data. The most noteworthy finding from these comparisons was that most of these foods contributed no net GRU, and that many contributed far more GSH than the foods containing only GRUs (Table 1).

A relatively small number of food items, many of which were purified or processed, contained no GSH or GRUs (Table 4). These items were from 9 food groups and included all soft drinks, 8.9% of all vegetable items, and 8% of all fruit items.

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
The present study showed that reactive chemicals are widely distributed among food groups and that the distribution differs considerably from that of GSH. The present study did not define the nature of the reactive chemicals, but they doubtlessly include a broad range of specific chemicals, including structurally diverse electrophiles, that have been studied individually and as groups of compounds by a large number of investigators. Because the toxicity of low concentrations of individual chemicals in food items is likely a function of the concurrent exposure to other reactive species, the classification of food items according to their GSH and GRU content should facilitate the identification of hazards from specific toxic exposures. For instance, the study identified some foods (e.g., blueberries, cherries, and prunes) that have relatively high concentrations of reactive chemicals, and others (e.g., freshly prepared meats) that have abundant levels of GSH and no GSH-reactive chemicals. These results imply that a specific reactive chemical may be a health risk if consumed with a diet high in GRUs but a lesser risk if consumed with a diet high in GSH.

Previous experimental data show that nutritional deficiencies that decrease GSH levels enhance the toxicity of reactive electrophiles, whereas inducers that increase GSH levels decrease susceptibility (20,21). In addition, chemicals that react with and deplete GSH enhance sensitivity to other toxic species, including peroxides, which can kill cells by apoptosis or necrosis. Consequently, we hypothesize that cellular toxicities linked to exposure to reactive chemicals may be a function of the intake of specific reactive chemicals, the intake of GSH and its precursors, and the total intake of GSH-reactive chemicals.

Some reactive electrophiles initiate and promote cancer development, but the measurement of concentrations of GSH-reactive chemicals used in the present study does not provide a measure of mutagenic or carcinogenic compounds in foods. Indeed, the transposition of information from food content to chemical properties to biological effects is complex. To investigate any association between the experimental data and the mutagenic activity of food items, we compiled data on mutagens in foods assayed with the Ames test without the inclusion of a bioactivating system (see supplementary data) (22–28). Several of the foods high in GRU were also positive, whereas many of the foods with highly negative net GRU levels were protective in assays with known mutagens. However, this comparison is anecdotal, and more rigorous analyses are needed.

Abundant evidence shows that tissue GSH is critical for protection against toxicity when cells are exposed to reactive species. Studies with rats and mice report that increased dietary GSH increases GSH in plasma (29) and some tissues (30), but quantitative studies indicate that this may be important in protection, principally under conditions of depleted tissue concentrations (30). However, dietary GSH provides an important source of GSH for detoxification in the intestinal tract and may be normally required for protection. Glutathione S-transferase, an enzyme that catalyzes the detoxification of electrophiles by GSH, is present in the mucus covering the extracellular surface of the small intestine (10), and the bile supplies GSH from the liver to the intestinal lumen (10). Thus, the data from the present study showing that reactive chemicals are widespread and common in foods suggest that the presence of GSH in the diet and/or the integrity of these endogenous mucosal defenses may be critical in protection against toxicity. This interpretation is supported by the earlier epidemiological report that dietary GSH intake is associated with decreased risk of oral cancer (14).

An alternative possibility is that exposure to reactive chemicals in the diet may be beneficial. Many reactive chemicals trigger detoxification systems; thus, the intake of foods containing GRUs could enhance protection. Such an effect could account for the association between GSH consumption and decreased relative risk of oral cancer observed only for GSH in fruits and vegetables (14). However, foods can contain protective chemicals other than GSH (such as antioxidant polyphenols, found in blueberries), and these could provide anticarcinogenic and other protective effects (31–33).

The experimental data provide a context for consideration of the possible risk associated with carcinogens such as acrylamide that occur in foods. Although acrylamide is mutagenic in vitro and carcinogenic in animal models, a population study found no association between dietary acrylamide and cancer (34). Previous analyses showed that dietary GSH concentrations are considerably higher (14) than acrylamide concentrations (3). The present study shows that the GRU concentration of many foods is similarly much greater than that of acrylamide. Thus, if the dietary intake of direct-acting carcinogens such as acrylamide presents a serious risk in humans, it is most likely to affect only a small subset of individuals, under conditions of concomitant intake of high net GRU levels in conjunction with impaired functioning of the endogenous GSH defenses.

In summary, the present study provides a relative quantification of reactive chemicals in foods, which can be used in conjunction with food frequency data to analyze the potential association between dietary intake of reactive chemicals and health risks. The distribution of reactive chemicals does not correspond to the usual food groupings and differs considerably from the distribution of GSH in foods. Analyses based on this data, along with consideration of the GSH concentration in foods, may elucidate the health risks and benefits associated with specific food items.

	FOOTNOTES

 
¹ This research was supported by the National Institutes of Health, Grant ES09047.

³ Abbreviations used: FDNB, 1-fluoro-2,4-dinitrobenzene; GRU, glutathione-reactive unit; GSH, glutathione; HHHQ, Health Habits and History Questionnaire.

⁴ Contents of GSH, GSH-reactive chemicals, and net GRU per gram of specific food items are included as supplemental data in the online posting of this article at www.nutrition.org.

Manuscript received 30 October 2003. Initial review completed 8 December 2003. Revision accepted 30 January 2004.

	LITERATURE CITED

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

1. Ames, B. N. (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221:1256-1264.[Abstract/Free Full Text]

2. Klaassen, C. D. eds. Casarett and Doull’s Toxicology 6th ed. 1996 Pergamon Press New York, NY. .

3. Food and Agriculture Organization/World Health Organization (2002) FAO/WHO Consultation on the Health Implications of Acrylamide in Food 2002 25–27 June 2002, Geneva, Switzerland (http://www.who.int/foodsafety/publications/chem/en/acrylamide_full.pdf).

4. Stadler, R. H., Blank, I., Varga, N., Robert, F., Hau, J., Guy, P. A., Robert, M. C. & Riediker, S. (2002) Acrylamide from Maillard reaction products. Nature 419:449-450.[Medline]

5. Mottram, D. S., Wedzicha, B. L. & Dodson, A. T. (2002) Acrylamide is formed in the Maillard reaction. Nature 419:448-449.[Medline]

6. Johnson, K. A., Gorzinski, S. J., Bodner, K. M., Campbell, R. A., Wolf, C. H., Friedman, M. A. & Mast, R. W. (1986) Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol. Appl. Pharmacol. 85:154-168.[Medline]

7. Damjanov, I. & Friedman, M. A. (1998) Mesotheliomas of tunica vaginalis testis of Fischer 344 (F344) rats treated with acrylamide: a light and electron microscopy study. In Vivo 12:495-502.[Medline]

8. Friedman, M. A., Dulak, L. H. & Stedham, M. A. (1995) A lifetime oncogenicity study in rats with acrylamide. Fundam. Appl. Toxicol. 27:95-105.[Medline]

9. Dearfield, K. L., Abernathy, C. O., Ottley, M. S., Brantner, J. H. & Hayes, P. F. (1988) Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity. Mutat. Res. 195:45-77.[Medline]

10. Samiec, P. S., Dahm, L. J. & Jones, D. P. (2000) Glutathione S-transferase in mucus of rat small intestine. Toxicol. Sci. 54:52-59.[Abstract/Free Full Text]

11. Hagen, T. M. & Jones, D. P. (1989) Role of glutathione on extrahepatic detoxication. Sakamoto, Y. Higashi, T. Taniguchi, N. Meister, A. eds. Glutathione Centennial: Molecular and Clinical Implications 1989:423-433 Academic Press New York, NY. .

12. Bai, C. & Jones, D. P. (1996) GSH transport and GSH-dependent detoxication in small intestine of rats exposed in vivo to hypoxia. Am. J. Physiol. 271:G701-G706.[Medline]

13. Jones, D. P., Coates, R. J., Flagg, E. W., Eley, J. W., Block, G., Greenberg, R. S., Gunter, E. W. & Jackson, B. (1992) Glutathione in foods listed in the National Cancer Institute’s Health Habits and History Food Frequency Questionnaire. Nutr. Cancer 17:57-75.[Medline]

14. Flagg, E. W., Coates, R. J., Jones, D. P., Byers, T. E., Greenberg, R. S., Gridley, G., McLaughlin, J. K., Blot, W. J. & Haber, M. et al. (1994) Dietary glutathione intake and the risk of oral and pharyngeal cancer. Am. J. Epidemiol. 139:453-465.[Abstract/Free Full Text]

15. Talalay, P. & Fahey, J. W. (2001) Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J. Nutr. 131:3027S-3033S.[Abstract/Free Full Text]

16. Reed, D. J., Babson, J. R., Beatty, P. W., Brodie, A. E., Ellis, W. W. & Potter, D. W. (1980) High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide and related thiols and disulfides. Anal. Biochem. 106:55-62.[Medline]

17. Jones, D. P., Carlson, J. L., Samiec, P. S., Sternberg, P., Jr, Mody, V. C., Jr, Reed, R. L. & Brown, L. A. (1998) Glutathione measurement in human plasma. Evaluation of sample collection, storage and derivatization conditions for analysis of dansyl derivatives by HPLC. Clin. Chim. Acta 275:175-184.[Medline]

18. Block, G., Dresser, C. M., Hartman, A. M. & Carroll, M. D. (1985) Nutrient sources in the American diet: quantitative data from the NHANES II survey. I. Vitamins and minerals. Am. J. Epidemiol. 122:13-26.[Abstract/Free Full Text]

19. Block, G., Dresser, C. M., Hartman, A. M. & Carroll, M. D. (1985) Nutrient sources in the American diet: quantitative data from the NHANES II survey. II. Macronutrients and fats. Am. J. Epidemiol. 122:27-40.[Abstract/Free Full Text]

20. Mannervik, B., Carlberg, I. & Larson, K. (1989) Glutathione: general review of mechanism of action. Dolphin, D. Avramovic, O. Poulson, R. eds. Glutathione. Chemical, Biochemical and Medical Aspects, part A 1989:475-516 Wiley New York, NY. .

21. Oleinick, N. L., Xue, L., Friedman, L. R., Donahue, L. L. & Biaglow, J. E. (1988) Inhibition of radiation-induced DNA-protein cross-link repair by glutathione depletion with L-buthionine sulfoximine. NCI Monogr. 6:225-229.

22. Green, M., Ben-Hur, E., Riklis, E., Gordin, S. & Rosenthal, I. (1980) Application of mutagenicity test for milk. J. Dairy Sci. 63:358-361.

23. Yamaguchi, T. (1989) Mutagenic activity of various kinds of cheese on the Ames, rec and umu assays. Mutat. Res. 224:493-502.[Medline]

24. Nagao, M., Takahashi, Y., Yamanaka, H. & Sugimura, T. (1979) Mutagens in coffee and tea. Mutat. Res. 68:101-106.[Medline]

25. Sterner, O., Bergman, R., Kesler, E., Magnusson, G., Nilsson, L., Wickberg, B., Zimerson, E. & Zetterberg, G. (1982) Mutagens in larger fungi. I. Forty-eight species screened for mutagenic activity in the Salmonella/microsome assay. Mutat. Res. 101:269-281.[Medline]

26. Nguyen, T., Fluss, L., Madej, R., Ginther, C. & Leighton, T. (1989) The distribution of mutagenic activity in red, rose and white wines. Mutat. Res. 223:205-212.[Medline]

27. Ikken, Y., Morales, P., Martinez, A., Marin, M. L., Haza, A. I. & Cambero, M. I. (1999) Antimutagenic effect of fruit and vegetable ethanolic extracts against N-nitrosamines evaluated by the Ames test. J. Agric. Food Chem. 47:3257-3264.[Medline]

28. Bala, S. & Grover, I. S. (1989) Antimutagenicity of some citrus fruits in Salmonella typhimurium. Mutat. Res. 222:141-148.[Medline]

29. Hagen, T. M., Wierzbicka, G. T., Sillau, A. H., Bowman, B. B. & Jones, D. P. (1990) Bioavailability of dietary glutathione. Effect on plasma concentration. Am. J. Physiol. 259:G524-G529.

30. Aw, T. Y., Wierzbicka, G. & Jones, D. P. (1991) Oral glutathione increases tissue glutathione in vivo. Chem. Biol. Interact. 80:89-97.[Medline]

31. Piga, A., Del Caro, A. & Corda, G. (2003) From plums to prunes: influence of drying parameters on polyphenols and antioxidant activity. J. Agric. Food Chem. 51:3675-3681.[Medline]

32. Wedge, D. E., Meepagala, K. M., Magee, J. B., Smith, S. H., Huang, G. & Larcom, L. L. (2001) Anticarcinogenic activity of strawberry, blueberry, and raspberry extracts to breast and cervical cancer cells. J. Med. Food 4:49-51.[Medline]

33. Roy, S., Khanna, S., Alessio, H. M., Vider, J., Bagchi, D., Bagchi, M. & Sen, C. K. (2003) Anti-angiogenic property of edible berries. Free Radic. Res. 36:1023-1031.

34. Mucci, L. A., Dickman, P. W., Steineck, G., Adami, H. O. & Augustsson, K. (2003) Dietary acrylamide and cancer of the large bowel, kidney, and bladder: absence of an association in a population-based study in Sweden. Br. J. Cancer 88:84-89.[Medline]

This Article Abstract Full Text (PDF) Data Supplement Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by He, M. Articles by Jones, D. P. Search for Related Content PubMed PubMed Citation Articles by He, M. Articles by Jones, D. P.