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Biomedical subjects

K Tomokuni

Publications and source records attributed to K Tomokuni.

At least 19 recordsLinked to original sources
PubMed2006

Decreasing urinary PAH metabolites and 7-methylguanine after smoking cessation.

OBJECTIVE: Humans are exposed to various carcinogens by smoking. Urinary metabolites of polycyclic aromatic hydrocarbons (PAH), one of the major carcinogens in cigarette smoke, were measured as the environmental carcinogen exposure marker for humans. We evaluated urinary exposure markers for smoking cessation. METHOD: In this study, we measured cigarette smoke exposure markers, such as urinary cotinine, PAH exposure markers, such as urinary 1-hydroxypyrene (1-OHP), 2-naphthol (2-NP) and 1-naphthol (1-NP), as well as a methylating chemical exposure marker, 7-methylguanine (7-MeG). The before smoking cessation levels of these markers, and the after smoking cessation levels were then compared. Eighteen subjects participated in this smoking cessation program. RESULTS: Levels of all of four markers were found to have decreased by 19-54% after smoking cessation. Urinary cotinine, 1-OHP, 2-NP and 7-MeG levels were found to have significantly decreased after smoking cessation. There were positive correlations between cotinine and three urinary PAH markers and between 1-OHP, 2-NP and 7-MeG. CONCLUSION: PAH metabolites were better biomarkers of smoking cessation than 7-MeG. Analyzing urinary metabolites or urinary DNA adducts is suitable for epidemiological studies.

Adult↗
PubMed2003

Leukocyte 8-hydroxydeoxyguanosine and aromatic DNA adduct in coke-oven workers with polycyclic aromatic hydrocarbon exposure.

OBJECTIVE: To investigate the potential for exposure to polycyclic aromatic hydrocarbons (PAHs) to induce oxidative DNA damage, we conducted a cross-sectional study in coke-oven workers employed at an iron-steel factory. METHODS: The study population contained 119 coke-oven workers from different work areas of the oven and 38 controls. Personal information on age, employment duration, smoking habit and alcohol consumption was obtained at an interview. Leukocyte 8-hydroxydeoxyguanosine (8-OHdG) was measured by high performance liquid chromatography with electrochemical detection. Leukocyte aromatic DNA adducts as effective dose, and urinary 1-hydroxypyren as internal dose, were also measured, and used to analyze the relationship of 8-OHdG with other biomarkers for PAH exposure, tobacco smoke and alcohol consumption. RESULTS: The leukocyte 8-OHdG revealed a wide inter-individual variation. The highest 8-OHdG level was detected in bottom-workers of the coke-oven. There were significant differences among the four different work areas ( P=0.02). We could not find significant correlation between 8-OHdG levels and urinary 1-hydroxypyrene, but a weakly positive correlation was found between 8-OHdG and leukocyte aromatic DNA adducts among all subjects (r=0.19 P=0.03). We could not observe any effect of smoking and alcohol drinking on 8-OHdG production. CONCLUSION: We could not find clear evidence that PAH exposure induces oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes.

OBJECTIVES: To investigate the influence of personal lifestyle--such as smoking and alcohol consumption-on urinary 1-hydroxypyrene (1-OHP) concentrations in coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to evaluate the association of 1-OHP concentrations with the genetic polymorphism of several metabolic enzymes including cytochrome P-450 (CYP) 1A1 and glutathione S-tranferases (GSTs). METHODS: The study population contained 162 coke oven workers and 58 controls employed at the largest iron and steel factory in China. Personal data were collected at the interview. 1-OHP in urine was measured with high performance liquid chromatography with fluorescence detection. Genetic polymorphisms were identified by the polymerase chain reaction (PCR) method. RESULTS: A positive association between excretion of urinary 1-OHP and the levels of exposure to PAHs was confirmed. Those people who consumed >or=50 g/day ethanol had significantly higher 1-OHP excretion than did other coke oven workers (p<0.01). No significant difference in urinary 1-OHP was found between smokers and non-smokers, in both controls and exposed subjects. The variant homozygotes at exon 7 of the CYP1A1 gene had significantly higher urinary 1-OHP concentrations than other CYP1A1 genotypes among the exposed workers (p=0.03). There was less association between the concentrations of 1-OHP and the GSTM1, GSTP1, or GSTT1 polymorphism. CONCLUSIONS: The present study confirmed that urinary 1-OHP is a good biomarker for exposure to PAHs. Alcohol consumption affected urinary 1-OHP excretion. The variant genotypes of the CYP1A1 gene may result in the enhancement of PAH metabolites. It is helpful to understand the role of individual susceptibility on metabolism of carcinogens. These findings suggest that the modulating effect of individual lifestyle factors or genetic nature should be considered in future studies on occupational exposure to PAHs and in evaluating the health risk from harmful chemicals.

Adult↗
PubMed2000

Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes.

OBJECTIVE: This study investigates the effect of multiple factors, including exposure to polycyclic aromatic hydrocarbons (PAHs), lifestyle, genetic polymorphism of cytochrome P450 (CYP)1A1, glutathione transferase (GST)M1, GSTP1, N-acetyltransferase (NAT)2 and gene p53, as well as any family history of cancer, on DNA adduct levels in coke-oven workers. METHODS: Sixty-five coke-oven workers employed at the largest iron-steel factory in China were recruited for the study. Personal data were collected at the interview. DNA adduct levels in total white blood cells (WBCs) were detected using 32P-postlabeling techniques. Genetic polymorphisms were analyzed by polymerase chain reaction (PCR) methods. RESULTS: The subjects were divided into low and high exposure groups, according to personal exposure to PAHs. The mean adduct value was 1.57 (range 0.54 to 4.35) per 10(8) nucleotides. A tendency for increased levels of DNA adducts in the high exposure group was observed, compared with the low exposure group (P = 0.07). In the low exposure group, DNA adducts were found to be positively associated with urinary cotinine (r = 0.44, P = 0.01). The rare allele homozygotes of CYP1A1 showed significantly higher DNA adduct levels than those of other CYP1A1 genotypes. Individuals with the NAT2 wild type had significantly increased DNA adduct levels than those with other NAT2 genotypes in the high exposure group. The p53 genetic polymorphism revealed a significantly positive effect on DNA adducts formation. There was a significantly higher adduct level in the subjects with a family history of cancer than those without, in the high exposure category. CONCLUSIONS: Effects of several variables, such as smoking, genetic polymorphism of 2 CYP1A1, NAT2, and gene p53, and a family history of cancer on DNA adduct levels were found, suggesting that these variables should be considered when evaluating the genotoxic effect of occupational exposure to PAHs using WBCs DNA adducts.

Arylamine N-Acetyltransferase↗
PubMed1998

Effects of genetic polymorphism of metabolic enzymes, nutrition, and lifestyle factors on DNA adduct formation in lymphocytes.

Although cigarette smoking is one major determinant of lung carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens, nutrition, and lifestyle. Previous studies have shown that genetic polymorphism of metabolic enzymes and plasma micronutrients are associated with lung cancer risk. DNA adducts may serve as a molecular dosimeter for exposure to carcinogens. In this cross-sectional study, we analyzed the blood samples of 158 subjects to evaluate the effects of polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase M1 (GSTM1), T (GSTT), N-acetytransferase 2 (NAT2), and aldehyde dehydrogenase 2 (ALDH2) as well as the effects of plasma beta-carotene and alpha-tocopherol on lymphocyte DNA adducts measured by 32P-postlabeling analysis. The DNA adduct level of smokers (mean +/- SD, 1.26 +/- 0.79/10(8) nucleotides) was significantly higher than that of nonsmokers (0.87 +/- 0.33, P = 0.007). Smokers with CYP1A1 minor homozygotes and GSTM1 null genotypes had a significantly higher level of DNA adducts than those without (P = 0.027 for homozygotes, P = 0.049 for heterozygotes). Smokers with NAT2 minor homozygotes also tended to have a higher DNA adduct level than those with heterozygotes and wild alleles, but the difference was not statistically significant. The DNA adduct level of smokers with ALDH2 heterozygotes was significantly higher than that of smokers with minor homozygotes (P = 0.045). When smokers were divided into "high" and "low" groups according to mean level of plasma beta-carotene or alpha-tocopherol, in the low beta-carotene group, the subjects with CYP1A1 minor homozygotes had higher DNA adduct levels than those with other CYP1A1 genotypes. Smokers with GSTT null genotype and high beta-carotene tended to have a higher DNA adduct level than those with GSTT present and high beta-carotene (P = 0.07), and those with GSTT null genotype and low beta-carotene (P = 0.07). There was weak correlation between DNA adduct level and number of cigarettes smoked per day in the low plasma beta-carotene group (r = 0.28, n = 36, p < 0.1). These results suggested that polymorphisms of CYP1A1, GSTM1, T, NAT2, and ALDH2, and plasma beta-carotene may modulate the level of DNA adducts.

Adolescent↗
PubMed1998

Evaluation of organic solvent-induced inflammation modulated by neuropeptides in the abdominal skin of hairless rats.

In this study, the severity and time course of inflammation induced by 4 organic solvents (acetone, cyclohexane, toluene and m-xylene), and the effect of neuropeptides during the inflammation were investigated in the hairless rat abdominal skin. Plasma extravasation used as a parameter of inflammation was measured by Evans blue and 125I-bovine serum albumin (BSA). Total volume of plasma extravasation induced by 4 organic solvents in 240-min exposure was as follows: toluene > m-xylene > cyclohexane > acetone = 0. While hydrophobic solvents (toluene, m-xylene, cyclohexane) induced plasma extravasation, the hydrophilic solvent, acetone, did not induce plasma extravasation. It was suggested that the severity and time course of plasma extravasation depend on chemical characteristics of the organic solvents. In immunohistochemical study, substance P (SP)-immunoreactive nerve fibers (IRNF) and calcitonin gene-related peptide (CGRP)-IRNF were intact during 240-min exposure to acetone. In contrast, cyclohexane, toluene, and m-xylene reduced the number of SP-IRNF and CGRP-IRNF in 10 min exposure and further reduced immunoreactivity. In hairless rats treated with systemic capsaicin, the above plasma extravasation was significantly reduced, along with SP-IRNF and CGRP-IRNF; however, protein gene product 9.5 (PGP 9.5)-IRNF was nearly intact. These results indicated that certain organic solvents induce instance of inflammation that vary widely in terms of their severity and time course, and that these differences are correlated with neuropeptides.

Abdomen↗
PubMed1997

Relationship between plasma concentrations of beta-carotene and alpha-tocopherol and life-style factors and levels of DNA adducts in lymphocytes.

beta-Carotene and alpha-tocopherol have been thought to reduce risk of lung cancer. Whether beta-carotene and alpha-tocopherol influence human DNA adducts, indicators of biologically effective doses of carcinogens, has been seldom studied. In this cross-sectional study, we measured plasma beta-carotene and alpha-tocopherol in 192 healthy men and DNA adducts in lymphocytes in 104 of the subjects. Because genetic polymorphism of cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) has been associated with interference in formation of reactive intermediates and detoxification of polycyclic aromatic hydrocarbons, we also obtained data concerning genetic polymorphism of CYP1A1 and GSTM1. In multiple regression analysis, parameters such as alcohol consumed per day, high-density lipoprotein cholesterol, Quetelet index, and cigarettes smoked per day were correlated inversely, whereas age, plasma alpha-tocopherol, and intake frequency of fruits were correlated positively with plasma beta-carotene concentration. DNA adduct levels of high plasma beta-carotene or alpha-tocopherol groups were not significantly different from the DNA adduct levels of low plasma beta-carotene or alpha-tocopherol groups among current smokers or nonsmokers. In variant states of CYP1A1 or GSTM1 polymorphism, after controlling for effect of cigarettes smoked per day, no significant correlation was found between plasma beta-carotene or alpha-tocopherol and DNA adduct levels. These results indicated that alcohol consumption, cigarette smoking, and plasma alpha-tocopherol have a close relationship with plasma beta-carotene. The plasma beta-carotene and alpha-tocopherol were not likely to influence the level of DNA adducts in lymphocytes.

Adolescent↗
PubMed1996

Comparison between males and females with respect to the porphyrin metabolic disorders found in workers occupationally exposed to lead.

To elucidate the sex difference in porphyrin metabolic disorders induced by lead exposure, we determined plasma delta-aminolevulinic acid (ALA), urinary ALA, and urinary coproporphyrin (CP) in 298 lead-exposed workers (160 males and 138 females), and compared the data thus obtained. The use of fluorometric high-performance liquid chromatography (HPLC) method which is highly sensitive and specific made possible the measurement of ALA in a small volume (50 microliters) of plasma. The concentrations (mean +/- SD) of lead in blood (males: 55.1 +/- 12.9 micrograms/dl; females: 54.7 +/- 13.5 micrograms/dl) indicated that the intensity of occupational exposure to lead was almost equal in the two groups. However, the elevation of plasma ALA concentration and the increased urine ALA and CP excretion among these lead workers were much higher in females than in males, confirming the finding of a sex difference in the biological effect of human exposure. The difference in urine CP excretion was especially pronounced, the mean concentration of urinary CP in the female workers being 3.5-5 times higher than that in the male workers.

Adult↗
PubMed1996

Chronic lead exposure may inhibit endothelium-dependent hyperpolarizing factor in rats.

We designed experiments to determine the effect of chronic lead exposure on endothelium-dependent responses to acetylcholine (Ach) in rat isolated blood vessels. Male Wistar rats were maintained for 1 or 3 months with or without oral lead administration. Membrane potential and isometric tension were measured in mesenteric arteries. Ach caused concentration- and endothelium-dependent relaxation in rings with endothelium contracted with phenylephrine (PE). There was no significant difference in relaxation between lead-exposed and control animals. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), both endothelium-dependent hyperpolarization and relaxation to Ach were significantly reduced in animals from the 3-month lead-exposed group. In aorta from lead-exposed groups, endothelium-dependent relaxation to Ach was not significantly different from that of age-matched controls, whereas both were completely inhibited in the presence of L-NAME. The basal levels of cyclic GMP in the aorta were not affected by lead exposure regardless of duration. These data indicate that both endothelium-dependent hyperpolarization and L-NAME-resistant relaxation decrease with chronic lead exposure in rat mesenteric arteries and suggest that lead is an inhibitor or endothelium-derived hyperpolarizing factor (EDHF).

Acetylcholine↗
PubMed1995

[Metabolic fate of porphyrin and its precursors in porphyria and porphyrinuria].

The metabolic fate of porphyrins and its precursors in porphyria and porphyrinuria is discussed to understand their excretion into the feces or urine. Eight enzymes play important roles in the porphyrin pathway. An enzymatic defect at each step of heme synthesis will induce each typical form of porphyria with the exception of the first enzyme. Each porphyria is described according to the enzyme in the heme biosynthetic sequence. Lead, which disturbs two enzymes involved in the heme biosynthesis, is one of typical chemicals inducing porphyrinuria. Lead porphyrinuria is also described according to the enzymes in the pathway. The figure of porphyrin pathway, drawn in details in the present chapter, will make it easier to understand the heme biosynthetic pathway related to porphyria or porphyrinuria.

Aminolevulinic Acid↗
PubMed1995

[Delta-Aminolevulinic acid in urine (screening method)].

Various methods for determining urinary delta-aminolevulinic acid (ALA) have been devised by many investigators since 1956. This paper introduces a history of the methodology in the determination of urinary ALA and application of some methods. These methods can be divided into two groups; one group consists of colorimetric methods based on the color reaction of ALA-pyrrole with Ehrlich's reagent, and the other group consists of fluorometric methods, based on the fluorescence derivatization of ALA and its separation by HPLC. Colorimetric methods are convenient and inexpensive, while these are less specific. On the other hand, the fluorometric HPLC methods are highly sensitive and specific, while these are expensive because of the high cost of the instruments.

Aminolevulinic Acid↗
PubMed1994

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.

5'-Nucleotidase↗
PubMed1994

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.

Adult↗
PubMed1993

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.

Acetylglucosaminidase↗