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Influence of glutathione S-transferase polymorphisms on genotoxic effects induced by tobacco smoke

Selena Palma1, Tommaso Cornetta, Luca Padua

  • 1Section of Toxicology and Biomedical Sciences, ENEA Research Center, Casaccia, Via Anguillarese 301, 00060 Rome, Italy.

Mutation Research
|July 24, 2007
PubMed

Insights

Cigarette smoking causes DNA damage, with women smokers showing higher sensitivity. Genetic variations in glutathione S-transferases (GST) influence susceptibility to tobacco smoke genotoxicity.

Area of Science:

  • Environmental Health
  • Toxicology
  • Genetics

Background:

  • Tobacco smoke is a known human carcinogen, but the precise mechanisms of its genotoxicity are not fully understood.
  • Enzymatic metabolism of tobacco smoke constituents by phase-I and phase-II enzymes is crucial, yet genetic variations can impair detoxification.
  • Glutathione S-transferases (GST) play a key role in detoxifying xenobiotics, and their polymorphic variations may influence susceptibility to smoking-induced DNA damage.

Purpose of the Study:

  • To investigate the influence of glutathione S-transferase (GST) M1, T1, P1, and A1 genotypes on the genotoxic effects of cigarette smoking.
  • To assess the impact of smoking, gender, and age on DNA damage endpoints.
  • To explore potential gene-gene interactions in modulating susceptibility to tobacco smoke-induced genotoxicity.

Main Methods:

  • Assessed genotoxic effects using chromosomal aberration (CA) assay and micronucleus (MN) test on peripheral blood lymphocytes from 72 healthy Caucasians.
  • Determined genotypes for GST M1, T1, P1, and A1 using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).
  • Analyzed the association between smoking status, gender, age, GST genotypes, and DNA damage markers.

Main Results:

  • Both smoking and gender significantly influenced DNA damage; female smokers exhibited a higher frequency of chromosomal aberrations than male smokers.
  • Smokers showed a significant increase in bi-nucleated micronuclei (BNMN) frequency compared to non-smokers, influenced by age, gender, and genetic constitution.
  • Individuals with the GSTM1-null genotype displayed higher susceptibility to tobacco smoke-induced DNA damage. A combination of GSTP1 variant allele and GSTM1-positive genotype was associated with lower BNMN frequency, while GSTM1-null plus GSTP1-wild type genotypes showed the most damage.

Conclusions:

  • Female smokers are more susceptible to DNA damage from cigarette smoke.
  • Genetic polymorphisms in GST enzymes, particularly GSTM1 and GSTP1, significantly modulate individual susceptibility to smoking-related genotoxicity.
  • Understanding gene-gene interactions in detoxification pathways is crucial for a comprehensive understanding of cancer risk associated with environmental exposures like tobacco smoke.

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