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Related Experiment Videos

Chloroform bioactivation leading to nucleic acids binding.

A Colacci1, S Bartoli, B Bonora

  • 1Istituto Nazionale per la Ricerca sul Cancro, IST-Genova, Italy.

Tumori
|August 31, 1991
PubMed
Summary

Chloroform covalently binds to DNA, RNA, and proteins in rats and mice, indicating weak DNA initiation. Glutathione (GSH) enzymes play a key role in activating chloroform metabolites for binding.

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Area of Science:

  • Toxicology
  • Biochemistry
  • Molecular Biology

Background:

  • Chloroform is a volatile organic compound with known toxicological effects.
  • Understanding the metabolic activation and DNA binding of chloroform is crucial for assessing its genotoxic potential.

Purpose of the Study:

  • To investigate the in vivo covalent binding of chloroform to macromolecules (DNA, RNA, proteins) in rat and mouse organs.
  • To elucidate the role of enzymatic bioactivation, including cytochrome P450 and glutathione S-transferases (GSTs), in chloroform-DNA adduct formation.
  • To compare the bioactivation pathways in different organs and species.

Main Methods:

  • In vivo intraperitoneal injection of chloroform in rats and mice.
  • Analysis of covalent binding of radiolabeled chloroform to DNA, RNA, and proteins in various organs.

Related Experiment Videos

  • In vitro studies using cell-free systems with liver microsomal fractions and cytosolic GSTs from rat and mouse.
  • Quantification of Covalent Binding Index (CBI) for DNA.

    • Main Results:

    • Chloroform exhibited covalent binding to DNA, RNA, and proteins in vivo in both rat and mouse organs.
    • CBI values for liver DNA classified chloroform as a weak genotoxic initiator.
    • RNA and protein labeling were generally higher than DNA labeling across organs and species.
    • In vitro, chloroform was bioactivated by cytochrome P450 and particularly by mouse lung cytosolic GSTs, suggesting a role for glutathione (GSH).
    • Combined microsomal and cytosolic systems showed additive or synergistic bioactivation effects.

    Conclusions:

    • Chloroform can bind covalently to DNA, RNA, and proteins in vivo, with weak DNA initiating potential.
    • Glutathione S-transferases are significantly involved in the bioactivation of chloroform metabolites, contributing to their binding to DNA.
    • Enzymatic systems, including cytochrome P450 and GSTs, play a critical role in chloroform's genotoxicity.