Biomedical subjects
M Ichiba
Publications and source records attributed to M Ichiba.
Aromatic DNA adducts, micronuclei and genetic polymorphism for CYP1A1 and GST1 in chimney sweeps.
Aromatic DNA adducts in total white blood cells, cytochrome P450 (CYP) class 1A1 and glutathione transferase (GST1) class mu genotypes and micronuclei in T- and B-lymphocytes were studied in 69 full-time chimney sweeps and 35 controls, all male subjects. The sweeps had a higher (22%) but statistically non-significant increase in the level of DNA adducts as compared to the controls when all individuals independent of genotype were compared. The non-inducible CYP1A1 genotype, m1/m1, lacking a MspI restriction site at the 3' end of the gene, was associated with significantly higher adduct levels in the sweeps. Among the 26 sweeps with the combined genotype m1/m1 and GST1(-), a statistically significant 60% increase in median adduct levels was observed as compared with those 14 control subjects with the corresponding genotype. Smoking also showed a significant effect on the level of adducts. The effect on DNA adducts by sweeping, smoking and genotype appeared to be additive and independent of each other. DNA adducts in sweeps were moderately but statistically significantly correlated with micronuclei in both T- and B-lymphocytes. The correlation between adduct levels and micronuclei was most marked in T-lymphocytes of individuals lacking the GST1 gene.
The in vitro effect of 13 metals on the activity of erythrocyte pyrimidine 5'-nucleotidase (P5N).
The in vitro effect of 13 metal ions on the activity of erythrocyte pyrimidine 5'-nucleotidase (P5N) was investigated. Particular metals belonging to the boron group have recently been used as materials in a semi-conductor manufacturing. Of these metal ions, Ga exhibited no inhibition of erythrocyte P5N, while in extensively inhibited the erythrocyte P5N activity at concentrations of 10(-4) to 10(-3) M. In addition, the activity of erythrocyte P5N was inhibited by 90-96% when the metal ions such as Cu, Ag, Cd, Hg or Pb were added to the incubation mixture at concentrations of 10(-4) to 10(-3) M. On the other hand, there was no difference between sulfate and nitrate in the in vitro effect of the metal ions on the activity of erythrocyte P5N.
Postlabeling analysis of DNA adducts in white blood cells from lead smelter workers.
We analyzed DNA adducts levels in white blood cells from 14 lead smelter workers for the first time as an indicator of the effect of lead exposure and compared with some lead exposure indices to evaluate whether lead exposure induces DNA adducts significantly. DNA adducts were measured by the nuclease P1 enhanced 32P-postlabeling method. As the lead exposure indices, we chose blood lead (Pb-B), urinary delta-aminolevulinic acid (ALA) and erythrocyte protoporphyrin (FEP). The levels of DNA adducts had a weak positive correlation with urinary ALA concentration (r = 0.62), but not significant correlation with Pb-B and FEP. This result suggests that lead exposure might have the effect to remain DNA adducts. The inhibition of DNA repair system may be one reason. This preliminary study need be followed by extended surveys on lead exposure.
Urinary N-acetyl-beta-D-glucosaminidase and beta-aminoisobutyric acid in workers occupationally exposed to metals such as chromium, nickel, and iron.
To examine the relationships between the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and beta-aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.
Interrelation between urinary delta-aminolevulinic acid (ALA), serum ALA, and blood lead in workers exposed to lead.
Using a fluorometric HPLC method, we determined delta-aminolevulinic acid (ALA) in sera and urine samples from 16 lead workers with blood lead levels ranging from 19 to 107 microG/100 ml. The concentration of ALA in serum correlated highly with the urinary ALA concentration (gamma = 0.957 for ALA mg/1; gamma = 0.967 for ALA mg/g creatinine). The ALA concentrations in the serum of lead workers ranged from 11 to 151 micrograms/1 with a mean of 51 micrograms/1. In addition, the concentrations of urinary ALA (mg/g creatinine) and serum ALA micrograms/1) had a strong correlation with blood lead concentrations (gamma = 0.838 and 0.892, respectively). These data indicate that the measurement of serum ALA, as well as urinary ALA, is very useful for the biological monitoring of occupational lead exposure.
HPLC micro-method for determining delta-aminolevulinic acid in plasma.
Explore the source record for details and available documents.
Urinary excretion of 3,4-dimethylhippuric acid in workers exposed to 1,2,4-trimethylbenzene.
The urinary excretion of 3,4-dimethylhippuric acid (34DMHA), a 1,2,4-trimethylbenzene (124TMB) metabolite, was investigated in workers exposed to 124TMB vapor. The time-weighted average of exposure to 124TMB was determined with a diffusive sampler. For biological monitoring of exposure, urine samples were collected from individual workers and analyzed for metabolites by high-pressure liquid chromatography. The concentration of urinary 34DMHA had a positive correlation with the level of exposure to 124TMB (r = 0.72). The data suggest that 34DMHA is one of the useful indicators for biological monitoring of 124TMB exposure.
Erythrocyte nucleotides in lead workers.
We determined erythrocyte nucleotides levels in 22 lead workers with blood lead ranging from 8 to 78 micrograms/dl. Their erythrocyte pyrimidine 5'-nucleotidase (P5N) activity ranged from 19.4 to 3.4 mumol uridine/h per g hemoglobin. A significant elevation of erythrocyte pyrimidine nucleotides was found, and their contents correlated inversely with erythrocyte P5N activity and positively with blood lead concentration. In particular, the contents of uridine triphosphate (UTP) and cytidine triphosphate (CTP) exhibited a high correlation with P5N activity (r = -0.56, -0.54). However, its concentration in lead workers was estimated to be much lower than that in hereditary P5N deficiency.
Relation between urinary beta-aminoisobutyric acid excretion and concentration of lead in the blood of workers occupationally exposed to lead.
Urinary beta-aminoisobutyric acid (ABA) concentration was determined by fluorometric high performance liquid chromatography in 22 workers occupationally exposed to lead. The urinary excretion of ABA was increased with increasing exposure to lead. The excretion of urinary ABA had a significant correlation with concentration of lead in blood (Pb-B) (r = 0.581), similar to the correlation of Pb-B with urinary delta-aminolaevulinic acid (ALA) concentration (r = 0.563). The determination of urinary ABA concentration in workers exposed to lead, therefore, may offer a new approach for evaluating the health effect of lead.
Measurement of urinary delta-aminolevulinic acid (ALA) by fluorometric HPLC and colorimetric methods.
We devised a fluorometric HPLC method for determining delta-aminolevulinic acid (ALA) in the urine of lead-exposed workers. With this fluorometric HPLC method and the conventional colorimetric method, the concentrations of urinary ALA in 84 lead workers were determined and compared. In the measurement of urinary ALA at lower levels (< or = 5 mg/1), the value of urinary ALA obtained by the fluorometric HPLC method was much lower than that obtained by the conventional colorimetric method, indicating that the colorimetric method also measures urinary ALA-like compounds such as aminoacetone. On the other hand, the measurement of urinary ALA at higher levels (> 5 mg/1) demonstrated that the ALA value obtained by the fluorometric HPLC method corresponded well with that of the conventional colorimetric method. A correlation coefficient between the fluorometric HPLC method and the colorimetric method was 0.856 for 60 urine samples with ALA < or = 5 mg/1, and 0.996 for 24 urine samples with ALA > 5 mg/1.
Fluorimetric determination of hepatic delta-aminolevulinic acid synthase activity by high-performance liquid chromatography.
A fluorimetric method for measuring the activity of delta-aminolevulinic acid synthase (ALAS) in the liver of mice has been developed. The liver homogenate was used as the enzyme source. The final concentration of glycine (substrate) used for the assay was 100 mM. The delta-aminolevulinic acid (ALA) formed during incubation was converted into a highly fluorescent derivative by condensation with acetylactone and formaldehyde (application of the Hantzsch reaction). This derivative was completely separated from other fluorescent substances in the reaction medium, and it was determined using a high-performance liquid chromatograph equipped with a fluorescence monitor (370/460 nm). The activity of ALAS was expressed as nmol ALA formed per gram liver per hour.
Elevated urinary excretion of beta-aminoisobutyric acid and delta-aminolevulinic acid (ALA) and the inhibition of ALA-synthase and ALA-dehydratase activities in both liver and kidney in mice exposed to lead.
Urinary excretion of beta-aminoisobutyric acid (ABA) and delta-aminolevulinic acid (ALA) was investigated in mice exposed to lead (500 p.p.m.) in drinking water for 14 days. Concentrations of both urinary ABA and urinary ALA increased significantly in the lead-exposed mice. However, the degree of increasing excretion was higher in urinary ALA (10-fold of the control) than in urinary ABA (2-fold of the control). On the other hand, it was demonstrated that ALA dehydratase in liver and kidney is inhibited by exposure to lead, while ALA synthase in these tissues has no inhibitory effect.
[Evaluation of renal function in workers exposed to mixed aromatic hydrocarbons].
Explore the source record for details and available documents.
Comparison of hepatic delta-aminolevulinic acid (ALA) synthase and ALA dehydratase activities and urinary ALA excretion in different strains of male mice.
Explore the source record for details and available documents.
Studies on erythrocyte pyrimidine 5'-nucleotidase (P5N) test and its evaluation in workers occupationally exposed to lead.
An erythrocyte pyrimidine 5'-nucleotidase (P5N) test was performed for 171 workers occupationally exposed to lead. Erythrocyte P5N activity was markedly inhibited by exposure to lead. Among several biological indicators (erythrocyte P5N, delta-aminolevulinic acid dehydratase (ALAD), protoporphyrin (PROTO), urinary delta-aminolevulinic acid (ALA), coproporphyrin (COPRO)), the P5N activity had the highest correlation with the concentration of lead in blood (r = -0.77). A significant inhibition of erythrocyte P5N was found in groups of lead workers with blood-lead levels of more than 10 to 19 micrograms/dl. This P5N inhibition started before any changes occurred in urinary ALA and COPRO. A 45 to 50% inhibition of P5N corresponded to the blood-lead value (50 micrograms/dl) of the BEI recommended by ACGIH. In some lead workers, erythrocyte nucleotides (mainly CTP and UTP) were determined. The data indicated that a marked accumulation of these nucleotides had occurred, and their levels correlated negatively with P5N activity and positively with blood lead.
Effect of lead on the activity of erythrocyte porphobilinogen deaminase in vivo and in vitro.
The effect of lead on the activity of erythrocyte porphobilinogen deaminase (PBGD) in vivo and in vitro was investigated using blood specimens obtained from controls and lead-exposed workers. When lead nitrate was added to the incubation mixture at a final concentration of 10(-4) M, 83% inhibition of erythrocyte PBGD activity was found. However, in workers occupationally exposed to lead, no inhibition of erythrocyte PBGD activity was detected. This finding indicates that the erythrocyte PBGD test is not useful for evaluating exposure to lead in workers. In addition, the in vitro study confirmed that mercuric chloride strongly inhibits erythrocyte PBGD activity.
Tolerance to lead-induced porphyrin metabolic disorders following lead pretreatment in mice.
The protective effect of pretreatment with lead on lead-induced toxicity was investigated in mice, using some biological parameters such as urinary excretion of delta-aminolevulinic acid (ALA) and coproporphyrin, accumulation of erythrocyte protoporphyrin and inhibition of erythrocyte delta-aminolevulinic acid dehydratase; these are useful indicators for evaluating the effects on health of lead. It was demonstrated that pretreatment with a single intraperitoneal dose of 2 mg Pb/kg, 7 days prior to the challenge dose, prevents in part the increasing excretion of urinary ALA induced by a challenge exposure to lead (200 ppm) in the drinking water for 7 days.