- Email: [email protected]
Cadmium, lead and phytochemicals
Medical Hypotheses (2005) 65, 699–702
http://intl.elsevierhealth.com/journals/mehy
Cadmium, lead and phytochemicals Orkide Donma a, M. Metin Donma
b,*
a
Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey Ministry of Health, Suleymaniye Maternity and Children’s Education and Research Hospital, Istanbul, Turkey b
Received 15 February 2005; accepted 23 March 2005
Summary Some metals are essential, others are found as contaminants in foodstuffs. There is some doubt on the antioxidant nature of foods or beverages containing phytochemicals because of cadmium and lead in foods. Evidence from epidemiological and experimental data has found an association between high fruit and vegetable intake and low cancer risk. However, these foods may also contain high amounts of carcinogenic metals, e.g., cadmium and lead shown to interfere with the repair of DNA damage. In this context, healthy and harmful effects of some nutrients are debated. As the benefits of a diet rich in fruits and vegetables are emphasized, attempts for regular mass administration of single food should be done prudently. c 2005 Elsevier Ltd. All rights reserved.
Introduction Metals and phytochemicals are ingested simultaneously in diet. Some metals are essential for human nutrition; others are found as contaminants in foodstuffs. Epidemiological and experimental data have found an association between high fruit and vegetable intake and low cancer risk [1–9]. However, they may also contain high amounts of carcinogenic metals, e.g., cadmium (Cd), lead (Pb) shown to interfere with the repair of DNA damage. In this article, Cd and Pb in foods rich in phytochemicals and their effects on cancer as well as their interactions with other metals are re-
* Corresponding author. Tel.: +90 532 371 72 07; fax: +90 212 560 88 98. E-mail addresses: [email protected], donmaohm@ istanbul.edu.tr (M.M. Donma).
viewed. Paradoxes related to the ingestion of these foods, the risks caused by the presence of these metals are introduced.
Cadmium and lead: dietary carcinogens? Besides essential metals, toxic metals are also ingested daily by humans as part of their diet. Spinach and cauliflower concentrate Cd, while Pb is found in brussel sprouts [1,3–7,9]. Since these metals are reported as carcinogenic and/or mutagenic [10–12] and they are common in human diet, concern has arisen on their contribution to cancer.
Cadmium A route of exposure to the toxic element Cd is via the consumption of vegetables grown on Cd
0306-9877/$ - see front matter c 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2005.03.029
700 contaminated soil. In non-smokers, food is the most important route of Cd exposure [3,4,9,13]. Elevated Cd intake through vegetables is associated with high health risks [14–17]. Cd, a potent immunotoxic metal, induces DNA strand breaks, sister chromatid exchanges and chromosomal aberrations in human cells. The suppression of apoptosis by Cd may be a significant aspect of its carcinogenic mechanism. Cd leads to the enhanced production of reactive oxygen species (ROS) and exerts its effects on cellular structure and mechanisms by depleting glutathione and protein-bound sulfhydryl groups, resulting in increased oxidative stress [18,19]. Various sources, which may cause enhanced soil Cd levels, results in an augmentation in the plant uptake of Cd. This may lead to increase in dietary Cd intake. Processes that acidify soil (e.g., acid rain) also raise Cd concentrations in foodstuffs [14–16]. Since long-term occupational exposure to Cd may contribute to development of lung cancer, one should consider the potential risks, which may arise from Cd, due to massive ingestion of spinach, peanuts and cruciferous vegetables, e.g., cauliflower.
Lead Lead is considered as another potential human carcinogen. Mechanisms of Pb carcinogenicity include direct DNA damage, clastogenicity and inhibition of DNA synthesis or repair. Pb may also generate ROS and cause oxidative damage to DNA. Pb can substitute for Zn in several proteins, which function as transcriptional regulators, e.g., Zn finger [20]. The central nervous system effects of Pb on children seem not to be reversible [21]. The major sources of Pb for non-occupationally exposed adults are food and beverages; particularly vegetables, e.g., spinach, broccoli, brussel sprouts, cucumber [13,14,22,23]. Pb in wine is also very important [24]. A correlation was found between blood Pb levels and wine consumption of the individuals. Elevated levels of Pb in wine have been explained by several possible contamination sources such as air pollution caused by leaded gasoline, tin–Pb capsules used to cover the bottleneck and Pb migration from genuine Pb crystal wine glasses. Knowledge of the relationship between metabolic pathways and metals contributes to our understanding of the health risks caused by environmental and occupational exposure of metals [25–27]. Consideration of the simultaneous presence of Pb and phytochemicals in some foodstuffs may facilitate the diagnosis of different types of cancer.
Donma and Donma
Interactions among metals in diet Exposure to Pb and Cd seems to decrease Zn, an essential element. The difference in distribution patterns of Zn may affect the availability of Zn for the developing organisms. Cd may replace Zn in metallothionein and create a complex, which is very toxic to renal tubular cells. Gastrointestinal absorption of Cd increases during Fe and Zn deficiencies [5,28–30]. The enrichment of Zn and Se restrains the accumulation of Pb and Cd, enhances the absorption of some other nutritional elements, and improves trace element status in vegetables [31]. This is another interesting aspect of the interactions among the metabolisms of metals. Women and children with low serum Fe levels exhibit increased Cd absorption. This infers that the bioavailability of Cd is related to diet [29]. It is also known that the adequate stores of dietary Fe and Zn inhibit the absorption of Cd [6]. In developing countries, Fe and Zn deficiencies are quite common among pregnant women and in the pediatric population. Fe deficiency is the most common cause of anemia in children and pregnant women throughout the world. Fe deficiency is associated with the concomitant accumulation of toxic metals such as Cd and significantly increased Ni absorption suggesting that Ni ions use the Fe transport systems. Citrate recommended to facilitate the absorption of Fe, will also favor the tendency towards Cd toxicity. These data emphasize the importance of metal interactions and the difficulties met on the matter. There are also difficulties and complex interactions concerning Pb. Zn and Fe deficiencies enhance Pb toxicity by increasing Pb absorption. There are significant negative correlations between Pb and Zn as well as Pb and Fe levels [32]. Inverse associations between Pb and essential metals, e.g., Fe and Zn are thought provoking. High Pb levels associated with low Fe and Zn levels may affect intellectual capability of children. Also, it may lead to intrauterine growth retardation and children with low birth weight, important risk factors for the adult diseases, which may develop during the future life of the child [33]. Pb–Cd interactions are probably the most studied, affecting toxicity of both metals. Considering Fe and Zn deficiencies, which are world-wide health problems, increased Cd absorption during Fe deficiency, and increased Pb absorption during both Fe and Zn deficiencies, ingestion of particularly cruciferous vegetables may precipitate the signs, symptoms and damages through metal toxicities caused by metal deficiencies.
Cadmium, lead and phytochemicals
Are cadmium and lead in phytochemical containing foods threatening? Highly recommended cruciferous vegetables are striking examples for the simultaneous presence of phytochemicals and toxic metals in foodstuffs. Their anticarcinogenic properties have been attributed to their glucosinolate content and their breakdown products, e.g., isothiocyanates [34]. Cruciferous vegetables are also known to concentrate Cd and Pb. These metals are considered as potential human carcinogens. The mechanisms of metal-induced carcinogenesis may involve an induction of lipid peroxidation and an increase in free radical levels in the cells, following Pb or Cd exposure, suggesting the induction of genotoxicity and carcinogenicity by indirect interactions, e.g., oxidative stress, of these metals with DNA [10]. The interaction between Cd and Ca in bone, intestine and kidney may result in bone metabolism disorders. Furthermore, pregnancy and lactation are important physiological factors affecting bone metabolism in the mother. Lactation contributes to the decrease in bone mineral density and Cd exerts a precipitating effect on decreasing bone metabolism of mother, even in case of relatively low Cd intake [35]. Evidences associating human Cd exposure with cancers of the liver have indicated that the liver has been implicated as a target also in humans and noted the potential relevance between liver cells and Cd-induced oncogenic process. An involvement of Cd in bladder cancer has also been suggested [36,37]. Prostate cancer is the most common malignancy found in males. Toxins containing Cd are among the risk factors identified so far. Cd increases the risk of the cancer [11,38]. Lycopene, the red color of fruits and vegetables, particularly tomatoes, is suggested as a component responsible for lowering the risk of prostate cancer [23]. However, significant increases as well as differential Cd distribution and accumulation in tomato parts have also been detected. Many questions concerning the role of tomato products in prostate and other cancers arise. It is reported that this hypothesis requires additional research to establish a casual relationship [8,17]. Cd may be considered as a parameter, which enlightens complex associations related to the matter. These facts emphasize the importance of considering the simultaneous presence of phytochemicals and these toxic metals in fruits and vegetables highly recommended recently.
701
Conclusion The powerful antioxidant activity of phytochemicals suggests a protective role for these compounds in carcinogenesis. Fruits and vegetables rich in these compounds are highly recommended. However, these foods may contain also high amounts of carcinogenic metals, e.g., Cd and Pb shown to interfere with DNA repair. The presence of these metals in different plants leads to the conclusion that prolonged consumption of such vegetables and fruits as well as medicinal herbs may be detrimental to health. Since many questions remain on the matter, risk: benefit considerations should always be made on the basis of phytochemical and metal contents of the foodstuffs, particularly during pregnancy, lactation and childhood. The interactions between dietary metals, ROS, dietary phytochemicals and elements of informational metabolism add another dimension to this argument, make the matter more complicated, and require further wide-scaled research studies as well as fruitful discussions.
Hypothesis We hypothesize that Cd and Pb are the elements which threaten our health due to recommendation of high fruit and vegetable consumption as well as herbal products. The presence of these toxic metals in foods with high phytochemical content and their adverse effects on human health are widely underestimated.
Testing the hypothesis Concentrations of Cd and Pb should be determined concomitant with the phytochemical concentrations in fruits, vegetables, physiological fluids and/or tissues. Therefore, it would be easier to discuss the beneficial and adverse effects of a specific fruit, vegetable or herbal products in an integrated manner. By this means, the accumulation of large number of reports, which raise many questions in minds will be prevented.
Acknowledgment This work was supported by the Research Fund of the University of Istanbul. Project number: UDP – 155/27052003.
702
References [1] Donma O, Donma MM. Dietary metals, phytochemicals, and cancer. J Nutr 2003;133:3866. [2] Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med 2002;113:71S–88S. [3] Rojas E, Herrera LA, Poirier LA, Ostrosky-Wegman P. Are metals dietary carcinogens? Mutat Res 1999;443:157–81. [4] Dabeka RW, McKenzie AD, Lacroix GMA. Dietary intakes of lead, cadmium, arsenic and fluoride by Canadian adults: a 24-hour duplicate diet study. Food Addit Contam 1987;4:89–102. [5] Goyer RA. Nutrition and metal toxicity. Am J Clin Nutr 1995;61:646S–50S. [6] Caussy D, Gochfeld M, Gurzau E, Neagu C, Ruedel H. Lessons from case studies of metals: investigating exposure, bioavailability and risk. Ecotoxicol Environ Saf 2003;56:45–51. [7] World Health Organization. Arsenic in drinking water. Fact sheet No. 201. Geneva: World Health Organization; 2001. [8] Hadley CW, Miller EC, Schwartz SJ, Clinton SK. Tomatoes, lycopene, and prostate cancer: progress and promise. Exp Biol Med 2002;227:869–80. [9] Noel L, Guerin T, Kolf-Clauw M. Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health. Food Chem Toxicol 2004;42:1203–10. [10] Valverde M, Cristina T, Rojas E. Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA–metal interaction? Mutagenesis 2001;16:265–70. [11] de la Taille A, Katz A, Vacherot F, et al. Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements. Presse Med 2001;30:557–60. [12] Furst A. Can nutrition affect chemical toxicity? Int J Toxicol 2002;21:419–24. [13] Jarup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167–82. [14] Cui YJ, Zhu YG, Zhai RH, et al. Transfer of metals from soil to vegetables in an area near a smelter in Nanning. China Environ Int 2004;30:785–91. [15] Samsoe-Petersen L, Larsen EH, Larsen PB, Bruun P. Uptake of trace elements and PAHs by fruit and vegetables from contaminated soils. Environ Sci Technol 2002;36:3057–63. [16] Millis PR, Ramsey MH, John EA. Heterogeneity of cadmium concentration in soil as a source of uncertainty in plant uptake and its implications for human health risk assessment. Sci Total Environ 2004;326:49–53. [17] Moral R, Cortes A, Gomez I, Mataix-Beneyto J. Assessing changes in Cd phytoavailability to tomato in amended calcareous soils. Bioresour Technol 2002;85:63–8. [18] Shimada H, Shiao YH, Shibata M, Waalkes MP. Cadmium suppresses apoptosis induced by chromium. J Toxicol Environ Health A 1998;54:159–68. [19] Stohs SJ, Bagchi D, Hassoun E, Baghci M. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 2001;20:77–88.
Donma and Donma [20] Sibergeld EK, Waalkes M, Rice JM. Lead as a carcinogen: experimental evidence and mechanism of action. Am J Ind Med 2000;38:316–23. [21] Bellinger DC. Lead. Pediatrics 2004;113:1016–22. [22] Finster ME, Gray KA, Binns HJ. Lead levels of edibles grown in contaminated residential soils: a field survey. Sci Total Environ 2004;320:245–57. [23] Malmauret L, Parent-Massin D, Hardy JL, Verger P. Contaminants in organic and conventional foodstuffs in France. Food Addit Contam 2002;19:524–32. [24] Almeida CM, Vasconcelos MT. Lead contamination in Portuguese red wines from the Douro region: from the vineyard to the final product. J Agric Food Chem 2003;51:3012–23. [25] Kaufmann A. Lead in wine. Food Addit Contam 1998;15:437–45. [26] Guadagnino E, Gambaro M, Grammiccioni L, et al. Estimation of lead intake from crystalware under conditions of consumer use. Food Addit Contam 2000;17:205–18. [27] Donma O, Donma MM. Association of headaches and the metals. Biol Trace Elem Res 2002;90:1–14. [28] Pizent A, Jurasovic J, Telisman S. Serum calcium, zinc and copper in relation to biomarkers of lead and cadmium in men. J Trace Elem Med Biol 2003;17:199–205. [29] Robson M. Methodologies for assessing exposures to metals: human host factors. Ecotoxicol Environ Saf 2003;56:104–9. [30] Olajire AA, Ayodele ET, Oyedirdan GO, Oluyemi EA. Levels and speciation of heavy metals in soils of industrial southern Nigeria. Environ Monit Assess 2003;85:135–55. [31] He PP, Lv XZ, Wang GY. Effects of Se and Zn supplementation on the antagonism against Pb and Cd in vegetables. Environ Int 2004;30:167–72. [32] Richter J, Hajek Z, Pfeifer I, Subrt P. Relation between concentration of lead, zinc and lysozome in placentas of women with intrauterine foetal growth retardation. Centr Eur J Public Health 1999;7:40–2. [33] Donma MM, Donma O. Low birth weight: a possible risk factor also for liver diseases in adult life? Med Hypotheses 2003;61:435–8. [34] Verhoeven DTH, Verhagen H, Goldbohm RA, van den Brandt PA, van Poppel G. A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact 1997;103:79–129. [35] Ohta H, Ichikawa M, Seki Y. Effects of cadmium intake on bone metabolism of mothers during pregnancy and lactation. Tohoku J Exp Med 2002;196:33–42. [36] Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. Effects of cadmium on DNA (cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 2003;286:355–65. [37] Darewicz G, Malczyk E, Darewicz J. Investigations of urinary cadmium content in patients with urinary bladder carcinoma. Int J Urol Nephrol 1998;30:137–9. [38] Ekman P. Genetic and environmental factors in prostate cancer genesis: identifying high-risk cohorts. Eur Urol 1999;35:362–9.
http://intl.elsevierhealth.com/journals/mehy
Cadmium, lead and phytochemicals Orkide Donma a, M. Metin Donma
b,*
a
Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey Ministry of Health, Suleymaniye Maternity and Children’s Education and Research Hospital, Istanbul, Turkey b
Received 15 February 2005; accepted 23 March 2005
Summary Some metals are essential, others are found as contaminants in foodstuffs. There is some doubt on the antioxidant nature of foods or beverages containing phytochemicals because of cadmium and lead in foods. Evidence from epidemiological and experimental data has found an association between high fruit and vegetable intake and low cancer risk. However, these foods may also contain high amounts of carcinogenic metals, e.g., cadmium and lead shown to interfere with the repair of DNA damage. In this context, healthy and harmful effects of some nutrients are debated. As the benefits of a diet rich in fruits and vegetables are emphasized, attempts for regular mass administration of single food should be done prudently. c 2005 Elsevier Ltd. All rights reserved.
Introduction Metals and phytochemicals are ingested simultaneously in diet. Some metals are essential for human nutrition; others are found as contaminants in foodstuffs. Epidemiological and experimental data have found an association between high fruit and vegetable intake and low cancer risk [1–9]. However, they may also contain high amounts of carcinogenic metals, e.g., cadmium (Cd), lead (Pb) shown to interfere with the repair of DNA damage. In this article, Cd and Pb in foods rich in phytochemicals and their effects on cancer as well as their interactions with other metals are re-
* Corresponding author. Tel.: +90 532 371 72 07; fax: +90 212 560 88 98. E-mail addresses: [email protected], donmaohm@ istanbul.edu.tr (M.M. Donma).
viewed. Paradoxes related to the ingestion of these foods, the risks caused by the presence of these metals are introduced.
Cadmium and lead: dietary carcinogens? Besides essential metals, toxic metals are also ingested daily by humans as part of their diet. Spinach and cauliflower concentrate Cd, while Pb is found in brussel sprouts [1,3–7,9]. Since these metals are reported as carcinogenic and/or mutagenic [10–12] and they are common in human diet, concern has arisen on their contribution to cancer.
Cadmium A route of exposure to the toxic element Cd is via the consumption of vegetables grown on Cd
0306-9877/$ - see front matter c 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2005.03.029
700 contaminated soil. In non-smokers, food is the most important route of Cd exposure [3,4,9,13]. Elevated Cd intake through vegetables is associated with high health risks [14–17]. Cd, a potent immunotoxic metal, induces DNA strand breaks, sister chromatid exchanges and chromosomal aberrations in human cells. The suppression of apoptosis by Cd may be a significant aspect of its carcinogenic mechanism. Cd leads to the enhanced production of reactive oxygen species (ROS) and exerts its effects on cellular structure and mechanisms by depleting glutathione and protein-bound sulfhydryl groups, resulting in increased oxidative stress [18,19]. Various sources, which may cause enhanced soil Cd levels, results in an augmentation in the plant uptake of Cd. This may lead to increase in dietary Cd intake. Processes that acidify soil (e.g., acid rain) also raise Cd concentrations in foodstuffs [14–16]. Since long-term occupational exposure to Cd may contribute to development of lung cancer, one should consider the potential risks, which may arise from Cd, due to massive ingestion of spinach, peanuts and cruciferous vegetables, e.g., cauliflower.
Lead Lead is considered as another potential human carcinogen. Mechanisms of Pb carcinogenicity include direct DNA damage, clastogenicity and inhibition of DNA synthesis or repair. Pb may also generate ROS and cause oxidative damage to DNA. Pb can substitute for Zn in several proteins, which function as transcriptional regulators, e.g., Zn finger [20]. The central nervous system effects of Pb on children seem not to be reversible [21]. The major sources of Pb for non-occupationally exposed adults are food and beverages; particularly vegetables, e.g., spinach, broccoli, brussel sprouts, cucumber [13,14,22,23]. Pb in wine is also very important [24]. A correlation was found between blood Pb levels and wine consumption of the individuals. Elevated levels of Pb in wine have been explained by several possible contamination sources such as air pollution caused by leaded gasoline, tin–Pb capsules used to cover the bottleneck and Pb migration from genuine Pb crystal wine glasses. Knowledge of the relationship between metabolic pathways and metals contributes to our understanding of the health risks caused by environmental and occupational exposure of metals [25–27]. Consideration of the simultaneous presence of Pb and phytochemicals in some foodstuffs may facilitate the diagnosis of different types of cancer.
Donma and Donma
Interactions among metals in diet Exposure to Pb and Cd seems to decrease Zn, an essential element. The difference in distribution patterns of Zn may affect the availability of Zn for the developing organisms. Cd may replace Zn in metallothionein and create a complex, which is very toxic to renal tubular cells. Gastrointestinal absorption of Cd increases during Fe and Zn deficiencies [5,28–30]. The enrichment of Zn and Se restrains the accumulation of Pb and Cd, enhances the absorption of some other nutritional elements, and improves trace element status in vegetables [31]. This is another interesting aspect of the interactions among the metabolisms of metals. Women and children with low serum Fe levels exhibit increased Cd absorption. This infers that the bioavailability of Cd is related to diet [29]. It is also known that the adequate stores of dietary Fe and Zn inhibit the absorption of Cd [6]. In developing countries, Fe and Zn deficiencies are quite common among pregnant women and in the pediatric population. Fe deficiency is the most common cause of anemia in children and pregnant women throughout the world. Fe deficiency is associated with the concomitant accumulation of toxic metals such as Cd and significantly increased Ni absorption suggesting that Ni ions use the Fe transport systems. Citrate recommended to facilitate the absorption of Fe, will also favor the tendency towards Cd toxicity. These data emphasize the importance of metal interactions and the difficulties met on the matter. There are also difficulties and complex interactions concerning Pb. Zn and Fe deficiencies enhance Pb toxicity by increasing Pb absorption. There are significant negative correlations between Pb and Zn as well as Pb and Fe levels [32]. Inverse associations between Pb and essential metals, e.g., Fe and Zn are thought provoking. High Pb levels associated with low Fe and Zn levels may affect intellectual capability of children. Also, it may lead to intrauterine growth retardation and children with low birth weight, important risk factors for the adult diseases, which may develop during the future life of the child [33]. Pb–Cd interactions are probably the most studied, affecting toxicity of both metals. Considering Fe and Zn deficiencies, which are world-wide health problems, increased Cd absorption during Fe deficiency, and increased Pb absorption during both Fe and Zn deficiencies, ingestion of particularly cruciferous vegetables may precipitate the signs, symptoms and damages through metal toxicities caused by metal deficiencies.
Cadmium, lead and phytochemicals
Are cadmium and lead in phytochemical containing foods threatening? Highly recommended cruciferous vegetables are striking examples for the simultaneous presence of phytochemicals and toxic metals in foodstuffs. Their anticarcinogenic properties have been attributed to their glucosinolate content and their breakdown products, e.g., isothiocyanates [34]. Cruciferous vegetables are also known to concentrate Cd and Pb. These metals are considered as potential human carcinogens. The mechanisms of metal-induced carcinogenesis may involve an induction of lipid peroxidation and an increase in free radical levels in the cells, following Pb or Cd exposure, suggesting the induction of genotoxicity and carcinogenicity by indirect interactions, e.g., oxidative stress, of these metals with DNA [10]. The interaction between Cd and Ca in bone, intestine and kidney may result in bone metabolism disorders. Furthermore, pregnancy and lactation are important physiological factors affecting bone metabolism in the mother. Lactation contributes to the decrease in bone mineral density and Cd exerts a precipitating effect on decreasing bone metabolism of mother, even in case of relatively low Cd intake [35]. Evidences associating human Cd exposure with cancers of the liver have indicated that the liver has been implicated as a target also in humans and noted the potential relevance between liver cells and Cd-induced oncogenic process. An involvement of Cd in bladder cancer has also been suggested [36,37]. Prostate cancer is the most common malignancy found in males. Toxins containing Cd are among the risk factors identified so far. Cd increases the risk of the cancer [11,38]. Lycopene, the red color of fruits and vegetables, particularly tomatoes, is suggested as a component responsible for lowering the risk of prostate cancer [23]. However, significant increases as well as differential Cd distribution and accumulation in tomato parts have also been detected. Many questions concerning the role of tomato products in prostate and other cancers arise. It is reported that this hypothesis requires additional research to establish a casual relationship [8,17]. Cd may be considered as a parameter, which enlightens complex associations related to the matter. These facts emphasize the importance of considering the simultaneous presence of phytochemicals and these toxic metals in fruits and vegetables highly recommended recently.
701
Conclusion The powerful antioxidant activity of phytochemicals suggests a protective role for these compounds in carcinogenesis. Fruits and vegetables rich in these compounds are highly recommended. However, these foods may contain also high amounts of carcinogenic metals, e.g., Cd and Pb shown to interfere with DNA repair. The presence of these metals in different plants leads to the conclusion that prolonged consumption of such vegetables and fruits as well as medicinal herbs may be detrimental to health. Since many questions remain on the matter, risk: benefit considerations should always be made on the basis of phytochemical and metal contents of the foodstuffs, particularly during pregnancy, lactation and childhood. The interactions between dietary metals, ROS, dietary phytochemicals and elements of informational metabolism add another dimension to this argument, make the matter more complicated, and require further wide-scaled research studies as well as fruitful discussions.
Hypothesis We hypothesize that Cd and Pb are the elements which threaten our health due to recommendation of high fruit and vegetable consumption as well as herbal products. The presence of these toxic metals in foods with high phytochemical content and their adverse effects on human health are widely underestimated.
Testing the hypothesis Concentrations of Cd and Pb should be determined concomitant with the phytochemical concentrations in fruits, vegetables, physiological fluids and/or tissues. Therefore, it would be easier to discuss the beneficial and adverse effects of a specific fruit, vegetable or herbal products in an integrated manner. By this means, the accumulation of large number of reports, which raise many questions in minds will be prevented.
Acknowledgment This work was supported by the Research Fund of the University of Istanbul. Project number: UDP – 155/27052003.
702
References [1] Donma O, Donma MM. Dietary metals, phytochemicals, and cancer. J Nutr 2003;133:3866. [2] Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med 2002;113:71S–88S. [3] Rojas E, Herrera LA, Poirier LA, Ostrosky-Wegman P. Are metals dietary carcinogens? Mutat Res 1999;443:157–81. [4] Dabeka RW, McKenzie AD, Lacroix GMA. Dietary intakes of lead, cadmium, arsenic and fluoride by Canadian adults: a 24-hour duplicate diet study. Food Addit Contam 1987;4:89–102. [5] Goyer RA. Nutrition and metal toxicity. Am J Clin Nutr 1995;61:646S–50S. [6] Caussy D, Gochfeld M, Gurzau E, Neagu C, Ruedel H. Lessons from case studies of metals: investigating exposure, bioavailability and risk. Ecotoxicol Environ Saf 2003;56:45–51. [7] World Health Organization. Arsenic in drinking water. Fact sheet No. 201. Geneva: World Health Organization; 2001. [8] Hadley CW, Miller EC, Schwartz SJ, Clinton SK. Tomatoes, lycopene, and prostate cancer: progress and promise. Exp Biol Med 2002;227:869–80. [9] Noel L, Guerin T, Kolf-Clauw M. Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health. Food Chem Toxicol 2004;42:1203–10. [10] Valverde M, Cristina T, Rojas E. Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA–metal interaction? Mutagenesis 2001;16:265–70. [11] de la Taille A, Katz A, Vacherot F, et al. Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements. Presse Med 2001;30:557–60. [12] Furst A. Can nutrition affect chemical toxicity? Int J Toxicol 2002;21:419–24. [13] Jarup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167–82. [14] Cui YJ, Zhu YG, Zhai RH, et al. Transfer of metals from soil to vegetables in an area near a smelter in Nanning. China Environ Int 2004;30:785–91. [15] Samsoe-Petersen L, Larsen EH, Larsen PB, Bruun P. Uptake of trace elements and PAHs by fruit and vegetables from contaminated soils. Environ Sci Technol 2002;36:3057–63. [16] Millis PR, Ramsey MH, John EA. Heterogeneity of cadmium concentration in soil as a source of uncertainty in plant uptake and its implications for human health risk assessment. Sci Total Environ 2004;326:49–53. [17] Moral R, Cortes A, Gomez I, Mataix-Beneyto J. Assessing changes in Cd phytoavailability to tomato in amended calcareous soils. Bioresour Technol 2002;85:63–8. [18] Shimada H, Shiao YH, Shibata M, Waalkes MP. Cadmium suppresses apoptosis induced by chromium. J Toxicol Environ Health A 1998;54:159–68. [19] Stohs SJ, Bagchi D, Hassoun E, Baghci M. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 2001;20:77–88.
Donma and Donma [20] Sibergeld EK, Waalkes M, Rice JM. Lead as a carcinogen: experimental evidence and mechanism of action. Am J Ind Med 2000;38:316–23. [21] Bellinger DC. Lead. Pediatrics 2004;113:1016–22. [22] Finster ME, Gray KA, Binns HJ. Lead levels of edibles grown in contaminated residential soils: a field survey. Sci Total Environ 2004;320:245–57. [23] Malmauret L, Parent-Massin D, Hardy JL, Verger P. Contaminants in organic and conventional foodstuffs in France. Food Addit Contam 2002;19:524–32. [24] Almeida CM, Vasconcelos MT. Lead contamination in Portuguese red wines from the Douro region: from the vineyard to the final product. J Agric Food Chem 2003;51:3012–23. [25] Kaufmann A. Lead in wine. Food Addit Contam 1998;15:437–45. [26] Guadagnino E, Gambaro M, Grammiccioni L, et al. Estimation of lead intake from crystalware under conditions of consumer use. Food Addit Contam 2000;17:205–18. [27] Donma O, Donma MM. Association of headaches and the metals. Biol Trace Elem Res 2002;90:1–14. [28] Pizent A, Jurasovic J, Telisman S. Serum calcium, zinc and copper in relation to biomarkers of lead and cadmium in men. J Trace Elem Med Biol 2003;17:199–205. [29] Robson M. Methodologies for assessing exposures to metals: human host factors. Ecotoxicol Environ Saf 2003;56:104–9. [30] Olajire AA, Ayodele ET, Oyedirdan GO, Oluyemi EA. Levels and speciation of heavy metals in soils of industrial southern Nigeria. Environ Monit Assess 2003;85:135–55. [31] He PP, Lv XZ, Wang GY. Effects of Se and Zn supplementation on the antagonism against Pb and Cd in vegetables. Environ Int 2004;30:167–72. [32] Richter J, Hajek Z, Pfeifer I, Subrt P. Relation between concentration of lead, zinc and lysozome in placentas of women with intrauterine foetal growth retardation. Centr Eur J Public Health 1999;7:40–2. [33] Donma MM, Donma O. Low birth weight: a possible risk factor also for liver diseases in adult life? Med Hypotheses 2003;61:435–8. [34] Verhoeven DTH, Verhagen H, Goldbohm RA, van den Brandt PA, van Poppel G. A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact 1997;103:79–129. [35] Ohta H, Ichikawa M, Seki Y. Effects of cadmium intake on bone metabolism of mothers during pregnancy and lactation. Tohoku J Exp Med 2002;196:33–42. [36] Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. Effects of cadmium on DNA (cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 2003;286:355–65. [37] Darewicz G, Malczyk E, Darewicz J. Investigations of urinary cadmium content in patients with urinary bladder carcinoma. Int J Urol Nephrol 1998;30:137–9. [38] Ekman P. Genetic and environmental factors in prostate cancer genesis: identifying high-risk cohorts. Eur Urol 1999;35:362–9.