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Carcinogenesis of β-Propiolactone: A Computational Study

Eva Španinger1, Urban Bren1

  • 1Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, SI-2000 Maribor, Slovenia.

Chemical Research in Toxicology
|February 15, 2020
PubMed

Insights

Beta-propiolactone (BPL) can damage DNA, but glutathione may protect against its harmful effects. Computer simulations reveal how BPL reacts with DNA bases and glutathione.

Area of Science:

  • Computational chemistry
  • Toxicology
  • Molecular biology

Background:

  • Beta-propiolactone (BPL) is a potential human carcinogen linked to tumor formation in animals.
  • Despite risks, BPL is used in vaccines for viral inactivation due to its efficacy.
  • Understanding BPL's reaction mechanisms is crucial for assessing its safety and applications.

Purpose of the Study:

  • To investigate the reaction mechanisms of BPL with DNA nucleobases and glutathione (GSH).
  • To elucidate the molecular interactions using quantum chemical methods and computer simulations.
  • To evaluate the potential protective role of GSH against BPL-induced DNA damage.

Main Methods:

  • Quantum chemical calculations were employed to simulate BPL reactions.
  • Solvent effects were incorporated to determine activation energies.
  • Reaction pathways (alkylation vs. acylation) and adduct formation were analyzed.

Main Results:

  • Guanine showed the highest reactivity towards BPL, forming adducts via an SN2 mechanism.
  • Alkylation was found to be energetically more favorable than acylation for all nucleobases.
  • Glutathione exhibited a high scavenging potential for BPL, comparable to guanine.

Conclusions:

  • Glutathione may act as a natural scavenger, protecting DNA from BPL.
  • This protective mechanism could mitigate BPL's genotoxicity, mutagenicity, and carcinogenicity.
  • The findings support the potential use of BPL in specific applications while highlighting protective biological mechanisms.

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