The effect of cellulose and glucomannan on the absorption of lead in rats]

The effect of two different fibers on lead (Pb) absorption was investigated during two 3-day balance-study periods (day 15th to 17th and 30th to 32nd) of a 32-day feeding course in young rats. Young rats were fed for 32 days diets containing Pb (200 mg/kg diet), with or without the addition of 10% cellulose or glucomannan. The following results were obtained: 1) The total fecal Pb content was significantly increased (p less than 0.05) in the Pb + cellulose group than in the Pb alone group during both balance-study periods. However, there was no significant difference between the Pb alone group and the Pb + glucomannan group. 2) Lead retention was significantly lower (p less than 0.05) in the Pb + cellulose group than in the Pb alone group during both balance-study periods. However, there was no significant difference observed between the Pb alone group and the Pb + glucomannan group. 3) Rats fed on the Pb + glucomannan diet had a significantly heavier (p less than 0.05) cecum and large intestine than rats fed on the other two diets. 4) The concentration of Pb in the cecum was significantly lower (p less than 0.05) in the Pb + cellulose group than in the other two groups. These results indicate that cellulose supplementation reduced the retention of Pb, while glucomannan supplementation had no significant effect on the retention of Pb.     

Lead levels in tissues from rats fed soils containing lead

Laboratory rats were fed soils containing elevated concentrations of lead. One soil was taken adjacent to a heavily traveled highway and one near a house that had been painted for many years with lead pigment paints. In addition, a third group of rats was fed lead acetate at a level in the diet similar to that in the diet of the rats fed soil. A fourth group of rats was fed a typical diet containing a normal amount of lead.Blood, bone, liver, kidney, and brain were analyzed for lead after 30 and 90 days of feeding. There was no statistically significant difference in blood lead levels between any of the groups. Similarly, brain and liver tissues showed no elevation in lead concentration compared to the controls except for the animals fed lead acetate that showed a slight elevation in lead in liver tissue at 30 days. Kidney tissue was elevated about 3- to 4-fold compared to controls, the rats fed lead acetate responding somewhat more than the rats fed soil lead. Bone tissue was elevated 3- to 5-fold compared to controls and at 90 days the rats fed lead acetate had higher bone lead levels than the rats fed soil. These results are compared to similar feeding studies reported in the literature. The greater response of tissue to lead in the earlier studies is thought to be due to a low bulk diet.The ALAD activity was measured in the blood of the rats. At 30 days the ALAD was not statistically lower than the controls, but at 90 days the rats fed lead were inhibited by approximately 20% compared to controls. Neither the lead-containing soil nor the lead acetate had an effect on the animal body weight gain or on the weight of liver, kidney, or brain. The retention of lead in bone and other tissues was very similar in the three dietary lead groups. The results of this feeding study indicate that these animals metabolize and handle the lead in different soils and from different sources in a very similar manner.     

The prevalence and retention of lead pellets in Japanese quail

Thirty-six Japanese quail (18 control birds, 18 lead-dosed birds) were used. The 18 quail were dosed with #4 lead weight that were orally inserted into the proventriculus. Delta-aminolevulunic acid dehydrase (ALAD) activity in erythrocytes in the dosed quail decreased 90% (p < 0.01) after one week as compared with the undosed quail. This inhibition of ALAD activity in erythrocytes indicates lead exposure. Radiographics were obtained at 0, 1, 4, 9, 22, and 32 days. The lead pellets remained in the gizzard and became smaller in 4 days. At day 22, after the lead treatment, in 8 quail of the treated quail 12, the lead pellets disappeared. At day 32, all lead pellets disappeared. These findings indicate that the ingested lead pellets are absorbed gradually in the intestine. The lead concentrations in the blood, liver, kidney, and femur of the lead-dosed quail were significantly higher than in the unclosed quail until the 6th week. At week 2, the lead concentration of the proventriculus, gizzard, gizzard contents, duodenum, small intestine, and cecum in the dosed quail was significantly higher. Lead concentration of feces was significantly higher at weeks 2 and 4 (p < 0.01). Throughout this study, no lead pellets were found in the feces.     

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.     

Postabsorptive effect of increased dietary zinc on toxicity and removal of tissue lead in rats

Weanling male albino rats were fed a diet containing 12 ppm zinc and 200 ppm lead for 3 weeks. At the end of this time a representative number of samples were collected to determine tissue zinc and lead, inhibition of the lead-sensitive liver enzyme delta-aminolevulinic acid dehydratase (ALAD), and urinary delta-aminolevulinic acid (ALA). Dietary lead exposure was terminated, and the remaining rats were fed diets containing either 12 or 200 ppm zinc. Analyses were repeated at 5-day intervals over a 15-day period after lead exposure. As expected, inhibition of liver ALAD, excretion of urinary ALA and soft tissue lead content rapidly decreased after lead was removed from the diet approaching control levels by day 15. Although high dietary zinc increased the zinc content of plasma, liver and tibia, there was little or no therapeutic effect on recovery of liver ALAD, urinary ALA excretion or on the removal of lead from liver, kidney or tibia. Removal of red blood cell lead, however, was greater for rats fed the high zinc diet. Results of this study indicate that the postabsorptive interaction between zinc and lead is considerably less important than the previously reported intestinal interaction.     

Effect of carbohydrates on lead absorption and retention in weanling rats

This study was designed to determine the effect of corn starch, lactose, and sucrose on lead (Pb) absorption and retention in rat tissues and organs. Seventy weanling Wistar male rats were assigned to the following five treatment groups: Group 1, 31.2% sucrose + 29.3% starch; Group 2, 31.2% lactose + 29.3% starch; Group 3, 60% corn starch (control); Group 4, 52.1% sucrose + 8.4% starch; Group 5, 52.1% lactose + 8.4% starch. All diets were supplemented with 200 ppm lead nitrate. The animals were fed the experimental diets for 8 weeks after which they were sacrificed. Analysis of lead in whole blood, bone (tibia and femur), carcass ash, and gut (alimentary canal) was done by atomic absorption spectrophotometric (AAS) technique. Results indicated that lactose in the diet caused increased lead retention by these tissues. Pb concentration was highest in blood (500% of the control) and bone (433% of control) of animals fed the Group 5 diet with the second highest level for the tissues of rats fed the Group 2 diet. Rats fed the high lactose diet showed the lowest weight gain and those fed the low sucrose diet showed the highest weight gain. The sucrose diets caused increased Pb in bone. In rats fed the sucrose diets, the Pb content of feces was greater than the value in rats fed the corn starch diet. The results of this study show that lactose has a higher stimulatory effect on Pb retention than sucrose.     

The effect of long-term fasting on the branched chain acylcarnitines and branched chain carnitine acyltransferases.

The effect of fasting for 8 days on the levels of carnitine acyltransferases in heart, liver, liver mitochondria, skeletal muscle, skeletal muscle mitochondria, kidney, and testes in young adult male rats was determined. The specific activities of acetyl-, octanyl-, isobutyryl-, and isovaleryl-carnitine acyltransferase in mitochondria isolated from the livers of fasted animals were significantly higher than the levels of the transferases isolated from livers of fed animals. Similar results were obtained with the 500 x g supernatant fluids from liver. In contrast, the specific activities of carnitine acyltransferases of 500 x g supernatant fractions isolated from heart, skeletal muscle, kidney, and testes were the same for fed as fasted animals. The total carnitine content of liver, muscle, heart, and kidney was less in animals fasted for 8 days than in fed animals, but the amount/g of organ was higher in the animals fasted for 8 days. The amount of specific short-chain acylcarnitines in liver, muscle, and heart was determined for both fed and fasted animals. The amount of isobutyrylcarnitine and isovalerylcarnitine increased significantly in muscle from fasted animals. These data are consistent with the previous suggestion that carnitine may have a role in the metabolism of the branched-chain amino acids.     

In vitro study on lead and alcohol interaction and the inhibition of erythrocyte delta-aminolevulinic acid dehydratase in man

The effect of lead (Pb) and ethanol (EtOH) interaction on the inhibition of erythrocyte delta-aminolevulinic acid dehydratase (ALAD) was investigated in human blood in vitro. Two different doses of ethanol (equivalent to 16.28 mmol of EtOH/l of blood and 108.53 mmol of EtOH/l of blood) and lead (equivalent to 2.17 mumol of Pb/l of blood and 4.34 mumol of Pb/l of blood) were examined separately and in combination. The dose-effect (EtOH-ALAD) relationship for a wide range of ethanol concentrations (0-217.06 mmol of EtOH/l of blood) was also investigated. The results obtained indicate that ethanol by itself does not inhibit ALAD, while lead does it readily. Neither ethanol concentrations significantly altered ALAD activity. The dose-effect (EtOH-ALAD) relationship did not reveal any inhibitory effect of ethanol on ALAD either; however, a weak trend towards increased ALAD activity was found. The effect of ethanol combined with lead indicated no significant difference as compared to the effect of the same dose of lead per se; however, a weak trend towards decreased ALAD activity was found. These findings support the hypothesis that the effect of ethanol on the transient inhibition of ALAD activity in vivo does not occur directly, but possibly through the intermediary action of lead from the body lead pool.     

Associations of patella lead with polymorphisms in the vitamin D receptor, delta-aminolevulinic acid dehydratase and endothelial nitric oxide synthase genes

A cross-sectional analysis was performed to evaluate associations of polymorphisms in the vitamin D receptor (VDR), delta-aminolevulinic acid dehydratase (ALAD), and endothelial nitric oxide synthase (eNOS) genes with patella lead concentrations in 652 lead workers in the Republic of Korea. There was a wide range of patella lead (from below detection limit to 946 microg Pb/g bone mineral), with a mean (standard deviation) of 75.2 (101.0). There were no associations of ALAD or eNOS genotypes with patella lead, but workers with the VDR B allele had significantly (P value < 0.05) higher patella lead (on average, 25% or approximately 6.6 microg Pb/g bone mineral) than lead workers with the VDR bb genotype. There was evidence that the relation between age and patella lead was modified by both the VDR and eNOS genotypes.     

Excretion of triethyl lead, diethyl lead and inorganic lead in the urine and feces of rabbits treated with diethyl lead dichloride

One group of rabbits were injected intraperitoneally with diethyllead dichloride (7.7 mg Pb/kg) and another group of rabbits were likewise injected with an equivalent lead dose of lead acetate. These rabbits were followed up for changes in the lead amounts excreted daily in the urine and feces from 24 h through 7 d after the injection, respectively. In the group of rabbits injected with diethyllead dichloride (one of 3 rabbits died during the observation), an amount of lead equivalent to about 25% of the injected dose was excreted in the urine during the first 24 h after the injection. Also, an amount of lead equivalent to about 28% of the injected lead was excreted in the feces during the first 3 d, and the total lead excretion during the 7 d after the injection corresponded to about 60% of the injected dose of diethyllead. One day after dosing, the total lead in the urine was made up of about 92% diethyllead, about 7% inorganic lead and about 1% triethyllead. One day after dosing, the total lead in the feces consisted of about 63% inorganic lead, about 28% diethyllead and about 9% triethyllead. Three days after dosing, the total lead in feces comprised about 98% inorganic lead, about 1% diethyllead and about 1% triethyllead. In the group of 3 rabbits injected with lead acetate, the total lead amount excreted in both the urine and feces during the 7 d after the injection corresponded to only about 9% of the injected dose of lead acetate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of feeding amaranth (food red no. 2) on the jejunal sucrase and digestion-absorption capacity of the jejunum in rats.

To clarify the effect of feeding 5% amaranth (Food Red No. 2, Am) alone or with 5% dietary fiber on jejunal mucosal integrity, change in jejunal sucrase activity before and after the feeding was compared between rats fed and fasted previously. Digestion-absorption capacity of the jejunum was also examined by perfusing 15 mmol/liter sucrose and 30 mmol/liter glycylglycine through the anesthetized rat jejunum after 14 days of feeding Am. Gobo dietary fiber (GDF) was prepared from the roots of edible burdock (Arctium lappa L.). At the end of 3 days' fasting, rats had 20% less body weight, 30% less mucosal protein and 50% less jejunal sucrase activity per unit length than those before fasting. Although rats fed Am showed severe diarrhea and growth retardation as observed in previous reports, initial sucrase level was not changed by feeding Am for 3 days even in the fasted rats. When sucrase activity on day 3 after feeding was compared among inter-groups, however, rats fed Am showed sucrase activity lower than that of rats fed either the basal diet or the basal diet containing Am plus GDF only when they had been fasted previously. After 14 days of feeding, rats fed Am after 3 days' fasting regained sucrase activity up to that of rats fed the basal diet despite the remarkable growth retardation. Jejunal perfusion in situ showed that digestion-absorption capacity for sucrose and glycylglycine in rats fed 5% Am for 14 days was also the same as that in rats fed the basal diet. These results suggest that feeding Am can reduce neither jejunal sucrase nor digestion-absorption capacity of epithelial cells of the jejunum, but retards the regain of the lowered sucrase level at earlier stage of feeding when rats have been fasted before the feeding, and that concurrent feeding of GDF promotes catch-up of the sucrase level lowered by the fasting.     

Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers.

The gene that encodes gamma-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 microg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 micromol/ml; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations >/= 40 microg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.     

Toxicology of ingested lead shot in ringed turtle doves

Ringed turtle doves ingested 0, 2, or 4 lead pellets and their blood was assayed for activity of the enzyme delta-aminolevulenic acid dehydratase (ALAD) at 24 hr and at sacrifice (14 days). At both blood sampling times, ALAD activity was reduced in the lead-treated birds concommitant with elevated blood lead concentrations. Hemoglobin concentration was not affected when assayed at sacrifice of the birds. Brain, liver, and kidney lead concentrations were significantly higher in doves that ingested lead shot. Approximately 70% of 110 mg lead pellets was eroded in the doves' gizzards in 14 days provided they were retained during that interval. Measurement of ALAD activity and blood lead offers potential for monitoring lead concentrations in wild mourning dove populations.     

Increased susceptibility to lead toxicity in rats fed semipurified diets

Rats fed stock diets, like Purina Chow, are known to be relatively insensitive to the toxic effects of lead. The addition of lead acetate (1000 ppm of Pb) to the drinking water of 5-week-old rats for 35 days produced toxicity (decreased growth rate and lead-induced anemia) in rats fed semipurified diet, but not in rats fed Purina Rat Chow (Chow). Blood and tissue lead levels also were higher in rats fed semipurified diet than in rats fed Chow. In order to determine whether rats fed semipurified diet could be used as animal models in the determination of permissible levels of lead in the environment, the susceptibility to lead toxicity of these rats to lead-based paints was tested. The addition of 1% paint chips containing 10% lead octoate to the diets resulted in lead toxicity (reduction in growth rates and hematocrit values) only in rats fed the semipurified diet. Rats fed a semipurified diet that permits normal growth are more susceptible to the toxic effects of lead and can be used more effectively in lead toxicity studies than rats fed Chow.     

Determination of delta-aminolevulinic acid dehydratase (ALAD) by enzyme immunoassay and its application to evaluation of lead exposure

Enzyme Immunoassay (EIA) technique using a glass bead was established in order to quantify the total amount of delta-aminolevulinic acid dehydratase (ALAD, EC 4, 2, 1, 24) including an inactivated enzyme and to determine the level of ALAD in erythrocytes of workers with moderate lead exposure. EIA was carried out by competitive antibody binding method in which the antigen (ALAD) was linked to a glass bead (O.D. 7 mm). A standard curve was fitted to the function y = A X B/(x-B) + C, where y is the enzymatic reaction product, x is the concentration of ALAD, and A, B and C are parameters. The coefficients of variation in the intra- and inter-assay were 3.7% and 6.5%, respectively. EIA-based amount of ALAD was 136.7 +/- 23 mg/l erythrocyte (mean +/- S.D.) in 66 workers. This ALAD amount was not found to be correlated with the lead level in the blood but correlated with the duration of lead-exposure. An especially good correlation (r = 0.453) was obtained with the inactivated portion of ALAD (EIA-based amount minus activity-based amount). On the other hand, the ratio of restored activity following heat treatment and addition of Zn and dithiothreitol to non-restored activity was well correlated with the lead level (r = 0.874), but not correlated with the duration of lead-exposure (r = 0.218). The inactivated portion of ALAD based on EIA accordingly may be considered a good indicator of the duration of lead exposure, and the activity-based amount of ALAD may be considered a suitable indicator of the extent of the present lead exposure.     

Effects of dietary restriction on cellular immunity in rats

Phagocytosis of opsonized sheep red blood cells (SRBC) by alveolar macrophages (AM) was measured in rats fasted for 1 to 9 days or fed on diets restricted 20 to 95% compared to control group for 2 and 8 weeks. In rats fasted for 1 to 6 days, AM showed an increased phagocytosis at 2 days after fasting, but their phagocytic activity remarkably decreased afterwards. Furthermore, phagocytic activity of AM per rat revealed much more decrease at 3 to 6 days after fasting. Then the production of interleukin-1 (IL-1) by AM increased with prolonged fasting, but the production of prostaglandin E2 (PGE2) by AM cultured with lipopolysaccharide (LPS) conversely decreased in rats fasted for 2 days or longer. The proliferation of splenocytes increased with prolonged fasting. On the other hand, 20 to 95% restricted diets induced the increased phagocytosis of AM with prolonged experimental period. However, phagocytic activity of AM per rat showed significant increase only in rats on a 40% restricted diet. The findings suggest that differences in both duration and degree of dietary restriction modulate phagocytic function of AM, and may contribute to explaining, in part, conflicting observations which have been obtained on the immunologic state in malnourished animals.     

Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers

Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.     

5-aminolevulinate dehydratase activity in blood of rabbits given tin or lead

The activity of 5-aminolevulinate dehydratase (ALAD) in rabbit blood is significantly inhibited by tin. Intravenous administration of tin (0.48 or 4.8 mumol/kg body weight) causes a decrease in the activity of the enzyme by 60% or 94% respectively. The effects of tin and lead on ALAD differ: inhibition by tin is not affected by pre-incubation at 50-60 degrees C, whereas the inhibitory effect of lead is increased by the same pretreatment. The optimum pH for rabbit blood ALAD is 6.8 in control rabbits. This optimum shifts to pH 5.8-6.0 in the blood of tin-treated rabbits, with or without pre-incubation at 60 degrees C for 5 min, while a similar shift is prevented by the same pre-incubation after lead treatment. Recovery to normal activity is faster after tin than after lead treatment.     

5-aminolevulinate dehydratase activity in blood of rabbits given tin or lead.

The activity of 5-aminolevulinate dehydratase (ALAD) in rabbit blood is significantly inhibited by tin. Intravenous administration of tin (0.48 or 4.8 mumol/kg body weight) causes a decrease in the activity of the enzyme by 60% or 94% respectively. The effects of tin and lead on ALAD differ: inhibition by tin is not affected by pre-incubation at 50-60 degrees C, whereas the inhibitory effect of lead is increased by the same pretreatment. The optimum pH for rabbit blood ALAD is 6.8 in control rabbits. This optimum shifts to pH 5.8-6.0 in the blood of tin-treated rabbits, with or without pre-incubation at 60 degrees C for 5 min, while a similar shift is prevented by the same pre-incubation after lead treatment. Recovery to normal activity is faster after tin than after lead treatment.     

Biomarkers of lead exposure

Biomarkers of exposure, effect, and susceptibility are reviewed in relation to lead exposure. Of the biomarkers of lead exposure, blood lead (Pb-B), mainly red cell lead, is a representative of soft tissue lead, and most widely used as measures of body burden and absorbed (internal) doses of lead. Urine lead (Pb-U) as well as plasma lead (Pb-P) increases exponentially with increasing Pb-B under a steady-state situation and is a reflection of recent exposure. The amount of lead in plasma and urine (MPb-P and MPb-U) after administration of a chelating agent (e.g. CaEDTA) can be useful for biomarkers of internal exposure of lead, reflecting the mobilizable pool of lead which consists of mainly blood and soft tissue lead with only a small fraction derived from bones. The critical effects in bone marrow arise mainly from the interaction of lead with some enzymatic process responsible for heme synthesis. The effects can be used for the biomarkers of effects. They are the inhibition of delta-aminolevulinic acid dehydratase (ALAD) and the variation in some metabolite concentrations (e.g. delta-aminolevulinic acid in urine (ALA-U), blood (ALA-B) or plasma (ALA-P), coproporphyrin in urine (CP), zinc protoporphyrin (ZP) in blood). The activities of pyrimidine nucleotidase (P5'N) and nicotinamide adenine dinucleotide synthetase (NADS) in blood are also decreased in lead exposure, and nucleotide contents in blood is altered in lead exposure. These effects of lead on human can be also useful biomarkers of effect. The differences in levels of heme precursors between two types of ALAD genotypes might be attributable to those in the affinity of different ALAD isozymes to lead. ALAD1 homozygotes have higher levels of ZP and ALA in comparison with ALAD2 carriers at the high lead exposure, suggesting that ALAD1 homozygotes might be more susceptible for disturbance in heme biosynthesis by lead than ALAD2 carriers.