Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101238455 Publication Model: Electronic Cited Medium: Internet ISSN: 1660-4601 (Electronic) Linking ISSN: 16604601 NLM ISO Abbreviation: Int J Environ Res Public Health Subsets: MEDLINE

Original Publication: Basel : MDPI, c2004-

Lead Poisoning* ; Occupational Exposure*/adverse effects ; Occupational Exposure*/analysis; DNA Repair ; Humans ; Lead/toxicity ; Porphobilinogen Synthase ; Recycling

Exposure to lead in environmental and occupational settings continues to be a serious public health problem. At environmentally relevant doses, two mechanisms may underlie lead exposition-induced genotoxicity, disruption of the redox balance and an interference with DNA repair systems. The aim of the study was to evaluate the ability of lead exposition to induce impaired function of Ape1 and its impact on DNA repair capacity of workers chronically exposed to lead in a battery recycling plant. Our study included 53 participants, 37 lead exposed workers and 16 non-lead exposed workers. Lead intoxication was characterized by high blood lead concentration, high lipid peroxidation and low activity of delta-aminolevulinic acid dehydratase (δ-ALAD). Relevantly, we found a loss of DNA repair capacity related with down-regulation of a set of specific DNA repair genes, showing specifically, for the first time, the role of Ape1 down regulation at transcriptional and protein levels in workers exposed to lead. Additionally, using a functional assay we found an impaired function of Ape1 that correlates with high blood lead concentration and lipid peroxidation. Taken together, these data suggest that occupational exposure to lead could decrease DNA repair capacity, inhibiting the function of Ape1, as well other repair genes through the regulation of the ZF-transcription factor, promoting the genomic instability.

Mutagenesis. 2001 May;16(3):265-70. (PMID: 11320153)
Toxicol Ind Health. 2022 Mar;38(3):139-150. (PMID: 35230206)
J Theor Biol. 2008 Mar 7;251(1):68-81. (PMID: 18082771)
Interdiscip Toxicol. 2012 Jun;5(2):47-58. (PMID: 23118587)
Front Pharmacol. 2021 Apr 13;12:643972. (PMID: 33927623)
Arch Toxicol. 2008 Aug;82(8):493-512. (PMID: 18496671)
Environ Health Perspect. 2004 May;112(7):799-804. (PMID: 15159209)
Biochem Biophys Res Commun. 2004 Jun 18;319(1):240-6. (PMID: 15158468)
Mol Carcinog. 2007 Feb;46(2):91-9. (PMID: 17013835)
Am J Ind Med. 2000 Sep;38(3):330-4. (PMID: 10940972)
Am J Ind Med. 2004 Dec;46(6):656-62. (PMID: 15551370)
Food Chem Toxicol. 2008 May;46(5):1488-94. (PMID: 18226849)
Biometals. 2005 Oct;18(5):493-506. (PMID: 16333750)
Int J Environ Res Public Health. 2022 Apr 03;19(7):. (PMID: 35409986)
Int J Hyg Environ Health. 2013 Aug;216(5):587-98. (PMID: 23540489)
Antioxid Redox Signal. 2009 Mar;11(3):601-20. (PMID: 18976116)
Toxicol Lett. 2002 Feb 28;127(1-3):47-54. (PMID: 12052640)
Mutagenesis. 2020 Feb 13;35(1):27-38. (PMID: 31816044)
Toxicol Lett. 2007 Sep 28;173(3):201-14. (PMID: 17855027)
Comput Struct Biotechnol J. 2021 Jun 24;19:3682-3691. (PMID: 34285771)
IARC Monogr Eval Carcinog Risks Hum. 2007;89:1-592. (PMID: 18335640)
Toxicol Rep. 2022 Feb 26;9:269-275. (PMID: 35256998)
Environ Sci Pollut Res Int. 2016 May;23(9):8244-59. (PMID: 26965280)
Free Radic Biol Med. 2013 Feb;55:63-72. (PMID: 23183323)
Environ Pollut. 2013 Oct;181:226-32. (PMID: 23872045)
Int J Dev Neurosci. 2003 Aug;21(5):235-44. (PMID: 12850056)
Environ Toxicol Pharmacol. 2014 Jan;37(1):45-54. (PMID: 24560336)
Environ Health Perspect. 2002 Dec;110 Suppl 6:931-41. (PMID: 12634122)
Exp Cell Res. 1988 Mar;175(1):184-91. (PMID: 3345800)
Environ Sci Pollut Res Int. 2018 Apr;25(12):12150-12158. (PMID: 29455351)
Z Klin Chem Klin Biochem. 1974 Aug;12(8):389-90. (PMID: 4428852)
Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:212-45. (PMID: 25795122)
Carcinogenesis. 2015 Jun;36 Suppl 1:S61-88. (PMID: 26106144)
Toxicol Ind Health. 2008 Oct;24(9):611-8. (PMID: 19106128)
Biomolecules. 2021 Oct 05;11(10):. (PMID: 34680095)
Toxicol Appl Pharmacol. 2014 Dec 1;281(2):195-202. (PMID: 25448684)
Mol Biosyst. 2016 May 26;12(5):1527-39. (PMID: 27063150)
Commun Biol. 2021 Jul 26;4(1):912. (PMID: 34312468)
J Cancer Prev. 2015 Dec;20(4):232-40. (PMID: 26734585)
Toxicol In Vitro. 2007 Sep;21(6):1121-6. (PMID: 17572058)
Biochem Med Metab Biol. 1990 Aug;44(1):37-41. (PMID: 2390288)
Environ Geochem Health. 2021 Jan;43(1):185-193. (PMID: 32813162)

Keywords: Ape1 activity; DNA-repair capacity; ZF-TF; comet assay; lead exposed workers; stress and toxicity gene profile

2P299V784P (Lead)
EC 4.2.1.24 (Porphobilinogen Synthase)

Date Created: 20220709 Date Completed: 20220712 Latest Revision: 20240831

20250114

PMC9265680

10.3390/ijerph19137961

35805621