For the purpose of determination the normal values of some parameters relevant to lead exposure, a study was carried out from April to June 30, 1986 on 258 healthy Korean adults who have had no apparent lead exposure. The lead indices subjected to this study were as follows; blood lead (PbB), hemoglobin (Hb), zinc protopprphyrin in blood (ZPP), delta-aminolevulinic acid dehydratase (ALAD) activity in blood, coproporphyrin in urine (CPU), delta-aminolevulinic acid in urine (ALAU). 1) The mean value of PbB was 17.17+/-7.87 microgram/100ml, and there was no statistically significant difference by age & sex. The distribution of PbB fitted to the log-normal distribution (chi-square=7.38, p>0.1). 2) The mean value of Hb in male (15.17+/-1.56g/100ml) was higher than in female (13.22+/-1.51 g/100ml)(p<0.01). The distribution of Hb fitted to the normal distribution (chi-square=9.40, p>0.1). 3) The mean value of ZPP was 32.61+/-8.78 microgram/100ml, and there was no statistically significant difference by age & sex. The distribution of ZPP fitted to the normal distribution (chi-square=13.93, p>0.05). The correlation of ZPP & ALAD (r=-0.229), CPU (r=0.183) was statistically significant respectively. 4) The mean value of ALAD was 30.20+/-10.96 mol ALA/min/L of R.B.C., and there was no statistically significant difference by age & sex. The distribution of ALAD activity did not fit to the normal distribution. The correlation between ALAD & PbB (r=-0.219) was statistically significant. 5) The mean value of CPU was 36.10+/-24.54 microgram/L, and there was no statistically significant difference by age & sex. The distribution of CPU did not fit to the normal distribution. The correlation between CPU & PbB (r=0.185), ZPP (r=0.183) was statistically significant respectively. 6) The meant value of ALAU was 1.94+/-0.96 ml/L, and there was no statistically significant difference by age & sex. The distribution of ALAU fitted to the normal distribution (chi-square=9.76, p>0.1).
Adult ; Aminolevulinic Acid ; Female ; Humans ; Male ; Porphobilinogen Synthase ; Reference Values* ; Zinc

A range of indicators is available to assess renal dysfunction in lead exposure. This study was undertaken to find out which indicators were most valuable as markers of renal dysfunction. We selected 75 male workers from the secondary lead smelter, plastic stabilizer and radiator manufacturing industries (the "exposed" group) and 64 male office workers (the "control" group). Blood lead; blood zinc protoporphyrin; urine lead; urine coproporphyrin; delta-aminolevulinic acid dehydratase activity; and urine delta-aminolevulinic acid were chosen as indicators of lead exposure. Blood urea nitrogen; serum creatinine; serum uric acid; urine N-acetyl-beta-D-glucosaminidase; urine albumin; urine alpha1-microglobu-lin; and urine beta2-microglobulin were used as indicators of renal dysfunction. Urine alpha1-microglobulin level was significantly associated with, the lead exposure level. Blood urea nitrogen, urine N-acetyl-beta-D-glucosaminidase and urine alpha1-microglobulin levels were highly correlated with indicators of lead exposure. Urine alpha1-microglobulin had the highest correlation with other indicators of renal function. In addition, the proportion of subjects with high urine alpha1-microglobulin levels showed a gradient with lead exposure. Conclusively, Blood urea nitrogen, urine N-acetyl-beta-D-glucosaminidase and urine alpha1-microglobulin are useful indicators, but urine alpha1-microglobulin is ; the early 'and the most valuable indicator of renal dysfunction related to lead exposure.
Acetylglucosaminidase ; Aminolevulinic Acid ; Blood Urea Nitrogen ; Creatinine ; Humans ; Male ; Plastics ; Porphobilinogen Synthase ; Uric Acid ; Zinc

A range of indicators is available to assess renal dysfunction in lead exposure. This study was undertaken to find out which indicators were most valuable as markers of renal dysfunction. We selected 75 male workers from the secondary lead smelter, plastic stabilizer and radiator manufacturing industries (the "exposed" group) and 64 male office workers (the "control" group). Blood lead; blood zinc protoporphyrin; urine lead; urine coproporphyrin; delta-aminolevulinic acid dehydratase activity; and urine delta-aminolevulinic acid were chosen as indicators of lead exposure. Blood urea nitrogen; serum creatinine; serum uric acid; urine N-acetyl-beta-D-glucosaminidase; urine albumin; urine alpha1-microglobu-lin; and urine beta2-microglobulin were used as indicators of renal dysfunction. Urine alpha1-microglobulin level was significantly associated with, the lead exposure level. Blood urea nitrogen, urine N-acetyl-beta-D-glucosaminidase and urine alpha1-microglobulin levels were highly correlated with indicators of lead exposure. Urine alpha1-microglobulin had the highest correlation with other indicators of renal function. In addition, the proportion of subjects with high urine alpha1-microglobulin levels showed a gradient with lead exposure. Conclusively, Blood urea nitrogen, urine N-acetyl-beta-D-glucosaminidase and urine alpha1-microglobulin are useful indicators, but urine alpha1-microglobulin is ; the early 'and the most valuable indicator of renal dysfunction related to lead exposure.
Acetylglucosaminidase ; Aminolevulinic Acid ; Blood Urea Nitrogen ; Creatinine ; Humans ; Male ; Plastics ; Porphobilinogen Synthase ; Uric Acid ; Zinc

OBJECTIVES: delta-Aminolevulinic acid dehydratase (ALAD) is a polymorphic enzyme that has two alleles, ALAD1 (ALAD1-1 as genotype) and ALAD2 (ALAD1-2 or ALAD2-2 as genotype). ALAD genotype has been reported to modify the pharmacokinetics and toxicity of lead. The authors investigated the influence of ALAD genotype polymorphism on renal function in lead workers METHODS: We studied 935 male lead workers and 87 male non-lead workers in the same industries. For cross-sectional renal indices, blood urea nitrogen (BUN), serum creatinine, serum uric acid and urine total protein were selected. Blood lead level was also measured an index of lead exposure. Information on weight, age, job duration, and smoking and drinking habits was collected. RESULTS: Whereas the mean blood lead level of lead workers was 25.4+/-10.9 microgram/dL, that of non-lead workers in the same premise was 10.1+/-2.8 microgram/dL, and the difference between the two groups was statistically significant. Whereas the prevalence of the variant allele, ALAD2 in 935 lead workers was 10.6%, that in 87 non-lead workers was 4.6%. However there was no difference of prevalence between the two groups. The mean blood lead level of subjects with ALAD1 was 23.9+/-11.4 microgram/dL, which was slightly lower than that of subjects with ALAD2 (25.8+/-10.7 microgram/dL). However, this difference was not statistically significant. After adjustment for the covariates, the subjects with ALAD2 allele were 12.8% less likely to have a median value or more of BUN than subject with ALAD1. The adjusted odds ratio was 0.59 (95% confidence interval; 0.38-0.91). After adjustment for the covariates, the subjects with ALAD2 allele were 9.3% less likely to have a median value or more of serum creatinine than subject with ALAD1. The adjusted odds ratio was 0.64 (95% confidence interval; 0.41-0.98). CONCLUSIONS: From the above results, it was found that the variant allele, ALAD2 appeared to modify the association of lead and renal function, and that ALAD2 genotype may be supportive for the protective effect of lead.
Alleles ; Blood Urea Nitrogen ; Creatinine ; Drinking ; Genotype* ; Humans ; Male ; Odds Ratio ; Pharmacokinetics ; Porphobilinogen Synthase ; Prevalence ; Smoke ; Smoking ; Uric Acid

Previous studies have suggested that delta-aminolevulinic acid dehydratase (ALAD) phenotype differently affect mineral metabolism. The objective of this study was to determine the effectiveness of 6-month iron supplementation as syrup of NaFeEDTA in improvement of iron status according to ALAD genotype. One hundred thirty adult women living in rural areas of Asan were provided NaFeEDTA syrup once a week for 6 months at the dose of 64mg Fe/week. Three hundred control subjects were observed during the study period. Fasting blood was obtained for analyzing hemoglobin (Hb) and zinc protophorphyrin (ZPP) and serum was analyzed for ferritin, iron and total iron capacity (TIBC) levels before and after iron supplementation. Ninety percent of ALAD 1-1 (ALAD1) and 10% of ALAD 1-2 (ALAD2) genotype were observed in the control group. However, in the intervention group, 98% showed ALAD1 while only 2% was ALAD2, which is significantly lower proportions of ALAD2 compared to the control group (p<0.01). The iron status of intervention group significantly improved except for ferritin and TIBC regardless of ALAD genotype, while the control group did not show any changes in iron status except for ZPP. ZPP concentration of the control group significantly increased in both ALAD1 and 2 while the intervention group showed significantly decreased ZPP after supplementation in ALAD1. Iron supplementation in the form of NaFeEDTA seems to be effective in reduction of ZPP levels although ALAD2 did not show significant changes due to the small number. However, it is difficult to make a conclusion from these results, and more specified further investigation is needed with more participants.
Adult ; Chungcheongnam-do ; Fasting ; Female ; Ferritins ; Genotype* ; Humans ; Clinical Trial* ; Iron* ; Metabolism ; Nutritional Status* ; Phenotype ; Porphobilinogen Synthase ; Zinc

OBJECTIVETo investigate the polymorphism of delta-aminolevulinic acid dehydratase(ALAD) and the genetic susceptibility to lead toxicity in Uighur and Yi population in China.

METHODSThe ALAD genotypes were determined by PCR and MspI restriction fragment length polymorphism techniques in 214 Uighur individuals from Xinjiang autonomous region and 144 Yi individuals from Yunnan province. The correlation between the polymorphism of ALAD and blood lead levels, and the factors affecting the latter were explored.

RESULTSThe frequencies of the allele ALAD1 and ALAD2 in Uighur are 0.91 and 0.09; and in Yi are 0.98 and 0.02 respectively. In Uighur the average blood lead level was (76 +/- 4) microgram/L, and 25.7% individuals with blood lead level > or = 100 micrograms/L. In Yi the average blood lead level was (50 +/- 16) microgram/L, and 6.3% individuals with blood lead level > or = 100 micrograms/L. However, no statistic correlation between the distribution of ALAD alleles and the blood lead level was found in both populations.

CONCLUSIONThe genetic susceptibility of ALAD polymorphism to lead toxicity may exhibit in a lead dose-dependent manner.

China ; ethnology ; Dose-Response Relationship, Drug ; Genetic Predisposition to Disease ; Humans ; Lead ; blood ; toxicity ; Polymorphism, Genetic ; Porphobilinogen Synthase ; genetics

OBJECTIVEThe objective of this study was to investigate arsenic induced changes in blood delta-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination.

METHODSRat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration.

RESULTSIn vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.

CONCLUSIONSThe results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Administration, Oral ; Animals ; Arsenic Poisoning ; blood ; Arsenicals ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Injections, Intraperitoneal ; Male ; Mice ; Porphobilinogen Synthase ; antagonists & inhibitors ; blood ; Rats ; Succimer ; analogs & derivatives ; pharmacology

OBJECTIVETo investigate the lead exposure, its effects, and the relationships between biomarkers of susceptibility in the workers with low-level occupational lead exposure, and to explore its sensitivity and practical value to evaluate the health hazard.

METHODSThe concentrations of lead fume and lead dust in workplaces of a lead acid storage battery enterprise in Jiangsu Province, China, were measured by occupational health monitoring method. The blood samples of 233 workers with occupational lead exposure and 76 non-occupational lead exposure were collected to measure the blood lead (Pb-B) level using graphite furnace atomic absorption spectrometry (GFAAS), the zinc Protoporphyrin (ZPP) level with blood fluorescence assay, and the delta-aminolevulinic acid dehydratase (ALAD) concentration by a spectrophotometer, and to determine the gene polymorphism of ALAD with TaqMan real-time polymerase chain reaction. At the same time, their urine samples were collected to measure urine lead (Pb-U) concentration with GFAAS and delta-aminolevulinic acid (ALA-U) concentration with a spectrophotometer. The correlations between the above indices were analyzed by multiple linear regression method.

RESULTSThe concentration of lead fume in 18 testing sites and the concentration of lead dust in 30 testing sites were 0.002-0.019 mg/m3 and 0.004-0.013 mg/m3, respectively. Pb-B level was positively correlated with Pb-U concentration (r=0.62, P<0.01) and ZPP level (r=0.47, P<0.01) and was negatively correlated with ALAD concentration (r=-0.77, P<0.01) in 233 workers with occupational lead exposure. Among 233 workers, 218 (93.6%) had ≤70 µg/L Pb-U, and 15 (6.9%) had ≥400≥g/L Pb-B. Pb-B level was not correlated with ZPP level as Pb-B level was <190 µg/L (r=0.18, P=0.068 ), while Pb-B level was positively correlated with ZPP level as Pb-B level was ≥190 µg/L (r=0.36, P<0.01). Pb-U concentration was positively correlated with ALA-U concentration (r=0.49, P<0.01) and ZPP level (r=0.47, P<0.01). ZPP level was negatively correlated with ALAD concentration (r=-0. 19, P<0.01), and was positively correlated with ALA-U concentration (r=0.27, P<0.01). ALAD concentration was not correlated with ALA-U concentration (r =-0. 11, P>0.05). And in 233 workers with occupational lead exposure, there were no significant differences in Pb-B level, ZPP level, and ALAD activity between the workers with ALAD1-2 genotype and the workers with ALAD1-1 genotype (P>0.05). In 76 workers with non-occupational lead exposure, there was no significant difference in Pb-B level between the workers with ALAD1-2 genotype and the workers with ALAD1-1 genotype (P >0.05). The workers with ALAD1-2 genotype had a significantly lower ALAD activity, and a significantly higher ZPP level compared with those ALAD1-1 genotype (P<0.01).

CONCLUSIONIn the workers with low-level occupational lead exposure, ZPP level is positively correlated with Pb-B level when Pb-B level was ≥190 µ/L. ALAD could be used as an effect biomarker of low Pb-B level. ALAD gene polymorphism shows different effects on the Pb-B level and the toxic effects between the workers with occupational lead exposure and the workers with non-occupational lead exposure.

Aminolevulinic Acid ; blood ; Biomarkers ; blood ; China ; Electric Power Supplies ; Genotype ; Humans ; Lead ; blood ; Linear Models ; Occupational Exposure ; Polymorphism, Genetic ; Porphobilinogen Synthase ; blood ; genetics ; Protoporphyrins ; blood

OBJECTIVEThe relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead.

METHODFour hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP.

RESULTSThe subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028).

CONCLUSIONSIt was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.

Alleles ; Body Height ; drug effects ; genetics ; Body Weight ; drug effects ; genetics ; Child ; China ; epidemiology ; Environmental Pollution ; adverse effects ; Female ; Gene Frequency ; Genotype ; Humans ; Lead ; adverse effects ; blood ; Lead Poisoning ; epidemiology ; etiology ; genetics ; Male ; Polymorphism, Genetic ; Porphobilinogen Synthase ; genetics ; Receptors, Calcitriol ; genetics