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Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
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Gastric DNA damage through tobacco chewing: in vitro mechanistic studies of DNA nitrite attack

Steven S Smith1, Roderich E Schwarz

  • 1Department of Tumor Cell Biology, City of Hope National Medical Center, Duarte, CA 91010, USA.

Cancer Letters
|June 11, 2005
PubMed

Insights

Chewing tobacco containing sodium nitrite can damage DNA, particularly at fragile sites. This DNA damage mechanism may contribute to gastric cancer initiation.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Genetics

Background:

  • Smokeless chewing tobacco is associated with upper aerodigestive organ cancers.
  • Nitrite in tobacco may promote DNA damage via carcinogenic mechanisms, especially at low pH.

Purpose of the Study:

  • To investigate the effect of sodium nitrite on DNA damage.
  • To examine DNA damage in single-strand conformers and hairpin loops at low pH.

Main Methods:

  • Studied the impact of sodium nitrite on DNA at pH 4.2.
  • Assessed DNA damage in hairpin loops versus Watson-Crick duplexes.
  • Analyzed reactivity of pyrimidine-rich and purine-rich DNA strands.

Main Results:

  • Two base-damage products were observed at significant levels (1-5% of total nucleotides).
  • Hairpin loops showed greater sensitivity to DNA damage than Watson-Crick duplexes.
  • Pyrimidine-rich DNA strands (e.g., CCG, CTG) were more reactive than purine-rich strands (e.g., CAG, CGG).

Conclusions:

  • Sodium nitrite induces DNA damage, particularly in hairpin loop structures.
  • The findings suggest an allele-specific predisposition to DNA damage.
  • This mechanism may play a role in gastric cancer initiation linked to chewing tobacco.

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