Carcinogenesis of β-Propiolactone: A Computational Study

Authors:
Open Access
Publisher website
Google Scholar
Abstract
The discovery that beta-propiolactone (BPL), once a commercially important chemical, causes various tumors in experimental animals has lead to a significant decrease in its use. However, owing to its efficacy this possible human carcinogen remains to be utilized in vaccines for inactivation of viruses. The focus of the current study was to uncover the mechanisms of beta-propiolactone reactions with both nucleobases and glutathione (GSH) through computer simulations based on quantum chemical methods. Our results, in accordance with in vitro studies, show that among all nucleobases guanine most readily forms adducts with BPL through SN2 reaction mechanism. Acquired activation energies with incorporated solvent effects reveal that alkylation represents an energetically more favorable reaction than acylation for all nucleobases. Comparison of activation free energies of glutathione and guanine reactions with BPL suggest that glutathione may represent an efficient natural scavenger of BPL. Therefore, glutathione present in the organism may provide protection to the DNA and thus prevent BPL’s genotoxicity, mutagenicity and possibly even carcinogenicity.
Funding Information
  • Ministrstvo za Izobra?evanje, Znanost in ?port (AB FREE, F4F)
  • The Slovenian Research and Innovation Agency (J1-5448, J1-6736)

This publication has 44 references indexed in Scilit: