ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, J. W.
Right arrow Articles by Kim, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, J. W.
Right arrow Articles by Kim, S. K.
Annals of Clinical & Laboratory Science 35:428-434 (2005)
© 2005 Association of Clinical Scientists

Relationships of Lead, Copper, Zinc, and Cadmium Levels versus Hematopoiesis and Iron Parameters in Healthy Adolescents

Jong Weon Choi1 and Soon Ki Kim2
1 Department of Laboratory Medicine and 2 Department of Pediatrics, College of Medicine, Inha University, Inchon, South Korea

Address correspondence to Jong Weon Choi, M.D., Ph.D., Department of Laboratory Medicine, Inha University Hospital, 7-206, 3-ga Shinheung-dong, Jung-gu, Inchon, 400-711, South Korea; tel 82 32 890 2503; fax 82 32 890 2529; e-mail jwchoi{at}inha.ac.kr.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
To investigate the relationships of trace element concentrations vs hematopoiesis and iron parameters, we measured lead, copper, zinc, cadmium, and ferritin levels in 251 healthy adolescents. Concentrations of trace metals were determined by atomic absorption spectrophotometry. There were no significant gender-related differences in serum copper or serum cadmium concentrations. However, blood lead and serum zinc levels were significantly higher in males than females (3.82 ± 1.24 and 118.4 ± 43.7 µg/dl vs 2.86 ± 1.06 and 83.5 ± 35.2 µg/dl, p <0.05, respectively). Subjects with elevated lead and copper concentrations exhibited significantly higher leukocyte counts and significantly lower serum iron levels than those with decreased lead and copper concentrations, but no significant differences were observed in blood erythrocyte counts or hemoglobin levels between the 2 groups. Blood lead concentrations were 2-fold higher in male adolescents with leukocytes >9.1 x 103/µl than in those with leukocytes <4.3 x 103/µl (5.04 ± 1.67 µg/dl vs 2.51 ± 0.75 µg/dl, p <0.05). Leukocyte counts had significant correlations with blood lead (r = 0.39, p <0.05) and serum copper (r = 0.26, p <0.05) in males and zinc (r = 0.28, p <0.05) in females. Serum iron levels were inversely correlated with blood lead and serum copper concentrations but were not correlated with serum zinc or cadmium levels. In short, blood lead and serum copper concentrations have important relationships to leukocyte counts and iron parameters in adolescents.

Keywords: lead, copper, zinc, cadmium, iron, ferritin, hematopoiesis, leukocytes


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Trace elements comprise metals in biological fluids at concentrations <1 µg/g of wet weight [1]. Among the trace elements, iron, copper, and zinc are involved in the function of several enzymes and are essential for maintaining health throughout life; lead and cadmium are non-essential toxic metals [2,3]. Trace elements can cause diseases through deficiency, imbalance, or toxicity. Trace mineral deficiencies usually occur when dietary intake is inadequate or result from metabolic imbalances produced by antagonistic or synergistic interactions among metals [4,5]. For instance, zinc absorption in small intestine is decreased by calcium, phosphate, and copper. On the other hand, excess zinc ingestion is a cause of copper deficiency [6].

There is an increasing recognition of the coexistence of multiple micronutrient deficiencies. Several investigators reported that blood lead concentrations are high in iron-deficient children [7], and that high dietary iron intake is associated with lower blood lead concentrations [8]. However, other researchers showed that iron depletion does not affect blood lead concentrations [9]. Interactions among trace elements and the relationships between blood lead concentration and iron parameters have been extensively studied [7–9], but few studies have closely examined associations of copper, zinc, and cadmium concentrations vs hematopoietic activities in healthy adolescents, especially in relation to body iron status. In the present study, we determined which hematologic index is most closely related to lead, copper, zinc, and cadmium levels in subjects who had no evidence of iron deficiency or iron-deficiency anemia. We also investigated whether the concentrations of trace metals show gender-related differences in adolescents.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This study was approved by the Committee of Ethics of the Inha University Hospital, and informed consent was obtained from all subjects. A total of 251 adolescents (122 males, 129 females) with a median age of 14 yr (range, 13–15 yr) were investigated by measurements of hemograms, serum iron parameters, and trace elements, including lead, copper, zinc, and cadmium. The investigation was conducted between 1 September 2004 and 15 October 2004. Subjects were all Korean students residing in municipalities without contaminated environments or industrial areas. To minimize the influence of age, smoking habits, and alcohol consumption on the concentrations of trace elements, only middle school students who had no histories of smoking or drug usage were enrolled. Non-anemic adolescents with a normal serum iron (>50 µg/dl) and serum ferritin levels (>12 µg/dl) were investigated because some trace elements can be affected by anemia or iron depletion [7]. Adolescents with a history of vitamin supplementation (n = 3) were excluded, as were those with recent infections (n = 2), since serum zinc levels can decrease in infections such as hepatitis [10].

After the subjects had fasted for >12 hr, blood samples were obtained by venipuncture using Vacutainer tubes (Becton-Dickinson, Franklin Lakes, NJ, USA). Blood lead levels were determined in 100 µl of EDTA-anticoagulated whole blood samples and the concentrations of copper, zinc, and cadmium were measured in serum specimens with an atomic absorption spectrophotometry (model 2380, Perkin-Elmer, Oak Brook, IL, USA). These assays are based on graphite furnace atomic absorption and have a high degree of accuracy [11]. Prior to assays of trace metals, the samples were refrigerated for no longer than 24 hr at 4°C. Complete blood cell counts were measured with EDTA-anticoagulated blood using an electronic counter (SE 9000, Sysmex, Kobe, Japan). Serum iron was assayed with a chemical analyzer (Hitachi 747; Hitachi, Tokyo, Japan) and ferritin was measured by a chemiluminescent method (ACS 180; Bayer Diagnostics, Tarrytown, NY, USA).

To investigate differences in blood cell counts and iron parameters in relation to trace element concentrations, subjects were assigned to the following groups: (i) males with lead <3.82 µg/dl (n = 64) and ≥3.82 µg/dl (n = 58), copper <98.2 µg/dl (n = 62) and ≥98.2 µg/dl (n = 60), and zinc <118.4 µg/dl (n = 59) and ≥118.4 µg/dl (n = 63); (ii) females with lead <2.86 µg/dl (n = 68) and ≥2.86 µg/dl (n = 61), copper <95.8 µg/dl (n = 63) and ≥95.8 µg/dl (n = 66), and zinc <83.5 µg/dl (n = 60) and ≥83.5 µg/dl (n = 69). The provisional cut-off levels applied in this categorization were based on mean concentrations of lead, copper, and zinc in male and female adolescents, respectively. To evaluate more strictly, we further stratified the adolescents into 2 groups based on those with leukocyte counts <10th percentile or >90th percentile leukocyte counts of all subjects: males with leukocytes <4.3 x 103/µl (10th percentile) and leukocytes >9.1 x 103/µl (90th percentile); females with leukocytes <4.2 x 103/µl (10th percentile) and leukocytes >9.2 x 103/µl (90th percentile).

Data analysis was performed using SAS statistical software (version 6.12, SAS Institute, Cary, NC, USA). A non-parametric test (Wilcoxon rank-sum test) was used to test the statistical significance of inter-group differences. Correlation coefficients were calculated by the Spearman method. All p values <0.05 were considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Mean values of trace element concentrations, iron parameters, and hemograms in subject populations are summarized in Table 1Go. Serum copper and serum cadmium concentrations showed a propensity toward high values in males compared to females, but the tendency was not statistically significant. However, blood lead and serum zinc concentrations averaged 3.82 ± 1.24 and 118.4 ± 43.7 µg/dl in males, which were significantly above the corresponding values (2.86 ± 1.06 and 83.5 ± 35.2 µg/dl, p < 0.05) in females.


View this table:
[in this window]
[in a new window]
  		Table 1. Trace element concentrations, iron parameters, and hematologic markers in healthy adolescents. The data are reported as means ± SD, with medians in brackets.
 
Males with elevated blood lead (≥3.82 µg/dl) and serum copper (≥98.2 µg/dl) concentrations exhibited significantly higher leukocyte counts [7.6 ± 1.7 and 7.8 ± 1.6 (x 103/µl) vs 5.9 ± 1.5 and 6.0 ± 1.4 (x 103/µl), p <0.05] and showed significantly lower serum iron levels (91.0 ± 28.1 and 89.9 ± 29.7 µg/dl vs 122.4 ± 33.1 and 120.3 ± 32.9 µg/dl, p< 0.05) than those with decreased values of the corresponding parameters (lead <3.82 and copper <98.2 µg/dl). However, there were no significant differences in erythrocyte counts and hemoglobin levels between the two groups (Table 2Go).


View this table:
[in this window]
[in a new window]
  		Table 2. Iron parameters and hematologic markers in relation to lead, copper, and zinc concentrations in male adolescents. The data are reported as means ± SD, with medians in brackets.
 
Serum iron concentrations were 85.1 ± 31.8 and 89.2 ± 29.6 µg/dl in females with elevated blood lead (≥2.86 µg/dl) or serum copper levels (≥95.8 µg/dl), respectively, which were significantly lower than in those (117.9 ± 36.5 and 118.7 ± 33.2 µg/dl, p <0.05) with decreased blood lead (<2.86 µg/dl) or serum copper levels (< 95.8 µg/dl) (Table 3Go). As shown in Table 4Go, males with increased leukocyte counts >9.1 x 103/µl (90th percentile) showed markedly high blood lead (5.04 ± 1.67 µg/dl) and serum copper (108.7 ± 21.5 µg/dl) concentrations, vs those with decreased leukocyte counts <4.3 x 103/µl (10th percentile) (2.51 ± 0.75 and 89.1 ± 19.6 µg/dl, p <0.05, respectively).


View this table:
[in this window]
[in a new window]
  		Table 3. Iron parameters and hematologic markers in relation to lead, copper, and zinc concentrations in female adolescents. The data are reported as means ± SD, with medians in brackets.
 

View this table:
[in this window]
[in a new window]
  		Table 4. Concentrations of trace elements in relation to leukocyte counts in male and female adolescents. The data are reported as means ± SD, with medians in brackets.
 
Correlation coefficients of hematologic markers and iron parameters vs trace element concentrations are summarized in Table 5Go. Leukocyte counts had significant correlations with blood lead (r = 0.39, p <0.05) and serum copper (r = 0.26, p <0.05) in males and serum zinc levels (r = 0.28, p <0.05) in females. Blood lead concentrations had negative correlation with serum iron levels (r = –0.32, p <0.05) and positive correlation with serum zinc concentrations (r = 0.27, p <0.05). Correlation coefficients between trace elements and serum iron levels were higher in males than in females for copper (r = –0.21 vs –0.15) and lead (r = –0.32 vs –0.19). No significant relations were noted between trace metal concentrations and hemoglobin levels.


View this table:
[in this window]
[in a new window]
  		Table 5. Correlation coefficients of hematologic markers and iron parameters vs trace element concentrations.
 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study shows that blood lead and serum copper concentrations have important relationships to blood leukocyte counts and serum iron parameters in adolescents. Our data are in partial agreement with a previous study, which demonstrated that white blood cell counts are significantly high in dogs and cats with increased blood lead levels [12]. Counter et al [13] reported that blood lead concentrations were higher in males than in females among children with chronic lead intoxication. Similarly, in our study blood lead and serum zinc concentrations were significantly higher in males than females. Clark et al [14] found that blood hemoglobin levels were significantly low in subjects with elevated blood lead concentrations [14]. Cohen et al [15] reported that elevated blood lead levels caused anemia by inhibition of hemoglobin production and shortened red cell survival.

In the present study, no significant differences were observed in blood hemoglobin levels between subjects with and without increase in blood lead levels. These apparent discrepancies may reflect the differences in blood lead concentrations of subject populations in the various studies. In general, blood lead levels in the range of 10 to 20 µg/dl are linked with adverse health effects, especially deleterious influences on hematopoietic, renal, endocrine, and reproductive systems [16]. On the other hand, in our study, blood lead concentrations ranged from 0.4–8.7 µg/dl in adolescents and there were no subjects with lead levels >10.0 µg/dl.

Interestingly, blood lead and serum copper levels correlated significantly with white blood cell counts but not with blood erythrocyte and hemoglobin levels. In particular, lead concentrations were 2-fold higher in male adolescents with moderately increased leukocyte counts than in those with decreased leukocyte counts. These results suggest that elevated blood lead and serum copper concentrations may be more closely associated with alteration in peripheral leukocyte numbers than with erythropoietic activities in healthy adolescents. To explain these findings, it is possible that subjects in this study included only non-anemic adolescents without iron depletion.

Nutritional deficiencies have been shown to increase the absorption and toxicity of orally ingested lead and cadmium [17]. Gastrointestinal lead absorption is enhanced by deficiency of iron, calcium, and zinc [18]. Oral ingestion of cadmium or lead perturbs the metabolism of zinc, copper, and iron and these changes may be the earliest manifestations of the toxicity of lead and cadmium [17]. In this study, subjects with elevated lead and copper concentrations revealed significantly lower serum iron levels than those with decreased lead and copper levels. Serum lead concentrations had negative correlations with serum iron levels and positive relationships with serum zinc concentrations. These data corroborate the results of our previous study, which demonstrated that iron deficiency constitutes a predisposing factor for lead poisoning and that elevated blood lead concentrations significantly diminished after iron supplementation in patients with iron-deficiency anemia [19].

The present study shows that blood lead concentration has a close association with serum iron levels in adolescents with no evidence of iron depletion or iron-deficiency anemia. These results suggest that minimal change in serum iron levels, even while subjects are in adequate iron balance, has an impact on blood lead concentrations. Taking these findings into consideration, it is plausible that gender-related difference in lead and zinc concentrations may be attributable to slight differences in serum iron and ferritin levels between males and females, although such differences were not statistically significant.

Toxic metals, such as lead and cadmium, interact metabolically with essential trace elements [20]. Chronic exposure to lead or cadmium contributes to a decrease of serum zinc levels in adult men [21]. Serum zinc levels have a negative effect on anemia by blocking the utilization of iron in the iron reserves of anemic subjects [22]. Cengiz et al [23] reported inverse correlations between serum zinc and copper levels in pregnant women during the second trimester. On the contrary, in the present study, no significant correlations were observed between serum zinc and copper levels, nor between serum cadmium and zinc levels. However, blood lead concentrations had significant correlations with serum zinc levels.

Relationships among the trace metals may be influenced by characteristics of subject populations, including age, gender, nutritional status, degree of exposure to environmental contamination, or behavioral habits. In fact, exposure to cadmium occurs mostly through smoking, while admitting that cadmium intoxication is related to industrial inhalation [21]. In our study, we investigated only non-smoking adolescents who had no history of chronic exposure to trace metals.

In conclusion, blood lead and serum copper concentrations were correlated significantly with blood leukocyte counts and serum iron levels but were not correlated with blood hemoglobin, erythrocyte counts, or serum cadmium levels, suggesting that the trace metals have important relationships to the lineage of hematopoietic cells and to iron metabolism. Correlation coefficients between trace elements and serum iron levels were higher in males than in females, indicating gender-related differences of trace metal metabolism in adolescents.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Reinhold JG. Trace elements: a selective survey. Clin Chem 1975;21:476–500.[Free Full Text]
  2. Delves HT. Assessment of trace element status. Clin Endocrinol Metab 1985;14:725–760.[Medline]
  3. Papageorgiou T, Zacharoulis D, Xenos D, Androulakis G. Determination of trace elements (Cu, Zn, Mn, Pb) and magnesium by atomical absorption in patients receiving total parenteral nutrition. Nutrition 2002; 18:32–34.[Medline]
  4. Harraki B, Guiraud P, Rochat MH, Alary J, Favier A. Interactions related to trace elements in parenteral nutrition. Pharm Acta Helv 1995;70:269–278.[Medline]
  5. Goldhaber SB. Trace element risk assessment: essentiality vs toxicity. Regul Toxicol Pharmacol 2003;38:232–242.[Medline]
  6. Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, Levinson BS, Bhushan V, Kroft SH. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005;123:125–131.[Medline]
  7. Bradman A, Eskenazi B, Sutton P, Athanasoulis M, Goldman LR. Iron deficiency associated with higher blood lead in children living in contaminated environments. Environ Health Perspect 2001;109:1079–1084.[Medline]
  8. Hammad TA, Sexton M, Langenberg P. Relationship between blood lead and dietary iron intake in preschool children. A cross-sectional study. Ann Epidemiol 1996;6: 30–33.[Medline]
  9. Hershko C, Konijn AM, Moreb J, Link G, Grauer F, Weissenberg E. Iron depletion and blood lead levels in a population with endemic lead poisoning. Isr J Med Sci 1984;20:1039–1043.[Medline]
  10. Selimoglu MA, Aydogdu S, Unal F, Yuce G, Yagci RV. Serum zinc status in chronic hepatitis B and its relationship to liver histology and treatment results. Pediatr Int 2001;43:396–399.[Medline]
  11. Bannon DI, Murashchik C, Zapf CR, Farfel MR, Chisolm JJ Jr. Graphite furnace atomic absorption spectroscopic measurement of blood lead in matrix-matched standards. Clin Chem 1994;40:1730–1734.[Abstract/Free Full Text]
  12. Berny PJ, Cote LM, Buck WB. Low blood lead concentration associated with various biomarkers in household pets. Am J Vet Res 1994;55:55–62.[Medline]
  13. Counter SA, Buchanan LH, Ortega F, Rifai N. Blood lead and hemoglobin levels in Andean children with chronic lead intoxication. Neurotoxicology 2000;21:301–308.[Medline]
  14. Clark M, Royal J, Seeler R. Interaction of iron deficiency and lead and the hematologic findings in children with severe lead poisoning. Pediatrics 1988;81:247–254.[Abstract/Free Full Text]
  15. Cohen AR, Trotzky MS, Pincus D. Reassessment of the microcytic anemia of lead poisoning. Pediatrics 1981;67: 904–906.[Abstract/Free Full Text]
  16. Bellinger DC, Stiles KM, Needleman HL. Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics 1992;90:855–861.[Abstract/Free Full Text]
  17. Petering HG. Some observations on the interaction of zinc, copper, and iron metabolism in lead and cadmium toxicity. Environ Health Perspect 1978;25:141–145.[Medline]
  18. Hashmi NS, Kachru DN, Khandelwal S, Tandon SK. Interrelationship between iron deficiency and lead intoxication. Biol Trace Elem Res 1989;22:299–307.[Medline]
  19. Choi JW, Kim SK. Association between blood lead concentrations and body iron status in children. Arch Dis Child 2003;88:791–792.[Abstract/Free Full Text]
  20. Goyer RA. Toxic and essential metal interactions. Annu Rev Nutr 1997;17:37–50.[Medline]
  21. 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.[Medline]
  22. Chirulescu Z, Suciu A, Tanasescu C, Pirvulescu R. Possible correlation between the zinc and copper concentrations involved in the pathogenesis of various forms of anemia. Med Interne 1990;28:31–35.[Medline]
  23. Cengiz B, Soylemez F, Ozturk E, Cavdar AO. Serum zinc, selenium, copper, and lead levels in women with second-trimester induced abortion resulting from neural tube defects: a preliminary study. Biol Trace Elem Res 2004;97:225–235.[Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, J. W.
Right arrow Articles by Kim, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, J. W.
Right arrow Articles by Kim, S. K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS