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Genetic polymorphisms and chromosome damage.

H Norppa1

  • 1Laboratory of Molecular and Cellular Toxicology, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. hannu.norppa@occuphealth.fi

International Journal of Hygiene and Environmental Health
|December 1, 2001
PubMed
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Genetic variations in detoxification enzymes like GSTM1 and NAT2 influence chromosome damage levels in exposed individuals. These genetic polymorphisms also impact baseline damage and in vitro genotoxicity, aiding in risk group identification.

Area of Science:

  • Environmental Health
  • Toxicology
  • Human Genetics

Background:

  • Genetic polymorphisms in xenobiotic metabolism and DNA repair pathways influence individual susceptibility to genotoxins.
  • Glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) are key polymorphic enzymes involved in detoxification.
  • Understanding these genetic variations can help identify individuals at higher risk and improve biomonitoring sensitivity.

Purpose of the Study:

  • To investigate the impact of genetic polymorphisms on chromosome damage and genotoxic response.
  • To evaluate the role of GSTM1, GSTT1, and NAT2 genotypes in human biomonitoring and in vitro genotoxicity testing.
  • To explore the potential significance of DNA repair gene polymorphisms in modulating genotoxic effects.

Main Methods:

Related Experiment Videos

  • Review of studies on genetic polymorphisms (GSTM1, GSTT1, NAT2, XRCC1) and their association with chromosome damage (DNA adducts, SCEs, CAs).
  • Analysis of human biomonitoring data from exposed populations (smokers, bus drivers).
  • Evaluation of in vitro genotoxicity test results from human cell cultures with different genotypes.

    • Main Results:

    • GSTM1 null genotype is associated with higher chromosome damage in exposed individuals.
    • GSTT1 and NAT2 null genotypes are linked to increased baseline levels of chromosome damage (SCEs, CAs).
    • GSTM1 and GSTT1 null genotypes increase in vitro sensitivity of human lymphocytes to genotoxins, notably diepoxybutane for GSTT1 null donors.

    Conclusions:

    • GSTM1, GSTT1, and NAT2 genetic polymorphisms significantly influence chromosome damage levels and genotoxic response.
    • These polymorphisms are valuable for identifying susceptible individuals and enhancing cytogenetic biomarkers.
    • Further research is needed to clarify the role of DNA repair gene polymorphisms, such as XRCC1, in genotoxic effects.