Abstract
Objective
The objective of this study was to evaluate the correlations of genetic polymorphism of genotypes δ-aminolevulinic acid dehydratase (ALAD), blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges (SCEs), and high SCE frequency cells (HFCs) in lead workers.
Methods
Three groups of lead workers were included in the study: high lead exposure group (26 workers), low lead exposure group (31 workers) and control group (30 controls who lived in an area uncontaminated by lead). Blood samples were taken from all subjects and analyzed for lead levels, ALAD genotype and SCE levels.
Results
Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin levels than the controls. There were no differences among the three groups regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2 genotype was not detected in any of the three groups. There were no significant differences among the three groups for BLLs, ZPP and hemoglobin levels based on ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P<0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the high lead exposure group than in the low lead exposure group (16.1%) and the control group (10%). There appeared to be an interaction effect on HFC percentages between smoking and lead exposure. When multiple regression analysis was used, the factors that affected SCE levels were lead exposure and smoking, but ALAD genotypes did not have any significant effect.
Conclusions
A significant association existed between both SCE and HFC levels and lead exposure. However, different ALAD genotypes were not found to be associated with levels of blood lead and ZPP in the three groups.
Similar content being viewed by others
References
Alexander BH, Checkoway H, Costa-Mallen P, Faustman EM, Woods JS, Kelsey KT, van Netten C, Costa LG (1998) Interaction of blood lead and δ-aminolevulinate acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers. Environ Health Perspect 106:213–216
Andersen O, Wulf HC, Ronne M, Nordberg GF (1982) Effects of metals on sister chromatid exchanges in human lymphocytes and Chinese hamster V79-E cells, In: Prevention of occupational cancer. ILO Occupational Safety and Health Series 46:491–450
Astrin KH, Bishop DF, Wetmur JG, Kaul B, Davidow B, Desnick RJ (1987) δ-Aminolevulinate acid dehydratase isozymes and lead toxicity. In: Mechanisms of chemically-induced porphyrinopathies. Ann N Y Acad Sci 514:23–39
Battistuzzi G, Petrucci R, Silagni L, Urbani FR, Caiola S (1981) δ-Aminolevulinate dehydratase: a new genetic polymorphism in man. Ann Hum Genet 45:223–229
Bauchinger M, Schmid E (1972) Chromosome analysis in cell cultures of the Chinese hamster after application of lead acetate. Mutat Res 14:95–100
Beek B, Obe G (1975) The human leukocyte test system, VI. The use of sister chromatid exchanges as possible indicators for mutagenic activities. Hum Genet 29:127–134
Bender MA (1989) Chromosomal aberration and sister chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. Mutat Res 212:149–154
Benkmann HG, Bogdanski P, Goedde W (1983) Polymorphism of delta-aminolevulinate acid dehydratase in various populations. Hum Hered 33:62–64
Bergdalh IA, Gerhardsson L, Schuts A, Desnick RJ, Wetmur JG, Skerfving S (1997a) Delta-aminolevulinate acid dehydratase polymorphism: influence on lead levels and kidney function in humans. Arch Environ Health 52:91-96
Bergdahl IA, Grubb A, Schutz A, Desnick RJ, Wetmur JG, Sassa S, Skerfving S (1997b) Lead binding to delta-aminolevulinic acid dehydratase in human erythrocytes. Pharmacol Toxicol 81:153–158
Carrano A V, Moore D H (1982) The rationale methodology for quantifying sister-chromatid exchanges in humans. In: Heddie JA (ed) New Horizons in genetic toxicology. Academic Press, New York, pp 267–304
Cooper WC (1976) Cancer mortality patterns in the lead industry. Ann N Y Acad Sci 27:150–176
Cullen MR, Kayne RD, Robins JM (1984) Endocrine and reproductive dysfunction in man associated occupational inorganic lead intoxication. Arch Environ Health 39:431–440
Dalpra L, Tibilletti G, Nocera G, Giulotto L, Auriti V, Carnelli V, Simoni G (1983) SCE analysis in children exposed to lead emission from a smelting plant. Mutat Res 120:249–256
Deknudt G, Manuel Y, Gerber GB (1977) Chromosomal aberrations in workers professionally exposed to lead. J Toxicol Environ Health 3:885–891
Douglas GR, Bell RDL, Grant CE, Wytsma JM, Bora KC (1980) Effect of lead chromate on chromosome aberration sister-chromatid exchanges and DNA damage in mammalian cells in vitro. Mutat Res 77:157–163
Forni G, Cambiaghi G, Secchi C (1976) Initial exposure to lead: chromosome and biochemical findings. Arch Environ Health 31:73–78
Fu H, Boffetta P (1995) Cancer and occupational exposure to inorganic lead compounds: a meta-analysis of published data. Occup Environ Med 52:73–81
Goto K, Maeda S, Kano Y, Sugiyama T (1978) Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma 66:351–359
Grandjean P, Wulf HC, Niebuhr E (1983) Sister chromatid exchange in response to variations in occupational lead exposure. Environ Res 32:199–204
Hartwig A, Schlepegrell R, Beyersmann D (1990) Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells. Mutat Res 241:75–82
Hsieh LL, Liou SH, Chen YH, Tsai LC, Yang T, Wu TN (2000) Association between aminolevulinate dehydratase genotype and blood lead levels in Taiwan. J Occup Environ Med 42:151–155
Huang XF, Feng ZY, Zhai WL, Xu JH (1988) Chromosomal aberrations and sister-chromatid exchanges in workers exposed to lead. Biomed Environ Sci 1:382–387
Kuo HW, Wang CS, Lai JS (1997) Semen quality in workers with long-term lead exposure: a preliminary study in Taiwan. Sci Total Environ 204:289–292
Lai JS, Kuo HW, Liao FC, Lien CH (1998) Sister chromatin exchange induced by chromium compounds in human lymphocytes. Int Arch Occup Environ Health 71:550–553
Perera FP, Santella RM, Brenner D, Poirier MC, Munshi AA, Fishman HK, van Ryzin J (1987) DNA adducts, proteins adducts and sister-chromatid exchange in cigarette smokers and non-smokers. J Natl Cancer Inst 79:449–456
Popenoe EA, Schmaeler MA (1979) Interaction of human polymerase β with ions of copper, lead, and cadmium. Arch Biochem Biophys 196:109–120
Potluri VR, Astrin KH, Wetmur JG, Bishop DF, Desnick RJ (1987) Human δ-aminolevulinate dehydratase: chromosomal localization to 9q34 by in situ hybridization. Hum Genet 76:236–239
Sarto F, Stella M, Acqua A (1978) Cytogenetic studies in 20 workers occupationally exposed to lead. Med Lav 69:172–180
Schmid E, Bauchinger M, Pietruck S, Hall G (1972) The cytogenetic effect of lead in human peripheral lymphocytes in vitro and in vivo. Mutat Res 16:401–406
Schütz S, Skerfving J, Ranstan JO, et al. (1987) Kinetics of lead in blood after the end of occupational exposure. Scand J Work Environ Health 13:221–231
Schwartz BS, Lee BK, Stewart W, Ahn Springer K, Kelsey K (1995) Association of δ-aminolevulinate acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers. Am J Epidemiol 142:738–745
Siemiatycki J (1991) Risk factors for cancer in the workplace. CRC Press, London
Sirover MA, Loeb LA (1976) Infidelity of DNA synthesis in vitro: screening for potential mutagens or carcinogens. Science 194:1434–1436
Skerfving S (1988) Biological monitoring of exposure to inorganic lead. In: Clarksun TW, Friberg L, Nordberg GF, Sager PR (eds) Biological monitoring of toxic metals. Plenum Press, New York, pp 169–198
Skreb Y, Habazin-Novak V (1975) Reversible inhibition of DNA, RNA, and protein synthesis in human cells by lead chloride. Toxicology 5:167–174
Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ (1986) Human δ-aminolevulinic acid dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A 83:7703–7707
Wetmur JG, Lehnert G, Desnick RJ (1991a) The δ-aminolevulinate dehydratase polymorphism: high blood lead levels in lead workers and environmentally exposed children with the 1-2 and 2-2 isozyme. Environ Res 56:109–119
Wetmur JG, Kaya AH, Plewinska M, Desnick RJ (1991b) Molecular characterization of the human δ-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning, Am J Hum Genet 49:757–763
Wu FY, Chang PW, Wu CC, Kuo HW (2002) Correlation of blood lead with DNA-protein crosslinks and sister chromatid exchange in lead workers. Cancer Epidemiol Biomarkers Prev 11:287–290
Wulf HC (1980) Sister chromatid exchanges in human lymphocytes exposed to nickel and lead. Dan Med Bull 27:40–42
Zelikoff J, Li JH, Hartwig A, Wang XW, Costa M, Rossman TG (1988) Genetic toxicology of lead compounds. Carcinogenesis 9:1727–1732
Ziemsen B, Angerer J, Lehnert G, Benkmann HG, Goedde HW (1986) Polymorphism of delta-aminolevulinate acid dehydratase in lead exposed workers. Int Arch Occup Environ Health 58:245–247
Acknowledgements
This study was supported by a National Science Council grant (NSC-89-2314-B-039-035).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wu, FY., Chang, PW., Wu, CC. et al. Lack of association of δ-aminolevulinic acid dehydratase genotype with cytogenetic damage in lead workers. Int Arch Occup Environ Health 77, 395–400 (2004). https://doi.org/10.1007/s00420-004-0517-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00420-004-0517-2