Correlation Investigation between Pyrrole-DNA and Pyrrole-Protein Adducts in Male ICR Mice Exposed to Retrorsine, a Hepatotoxic Pyrrolizidine Alkaloid

Lin Zhu, Junyi Xue, Yisheng He, Qingsu Xia, Peter P. Fu*, Ge Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

3 Citations (Scopus)

Abstract

Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Catalyzed by hepatic cytochrome P450 enzymes, PAs are metabolized into reactive pyrrolic metabolites, which can alkylate cellular proteins and DNA to form pyrrole-protein adducts and pyrrole-DNA adducts, leading to cytotoxicity, genotoxicity, and tumorigenicity. To date, the correlation between these PA-derived pyrrole-protein and pyrrole-DNA adducts has not been well investigated. Retrorsine is a representative hepatotoxic and carcinogenic PA. In the present study, the correlations among the PA-derived liver DNA adducts, liver protein adducts, and serum protein adducts in retrorsine-treated mice under different dosage regimens were studied. The results showed positive correlations among these adducts, in which serum pyrrole-protein adducts were more accessible and present in higher abundance, and thus could be used as a suitable surrogate biomarker for pyrrole-DNA adducts to indicate the genetic or carcinogenic risk posed by retrorsine.

Original languageEnglish
Article number377
Number of pages9
JournalToxins
Volume14
Issue number6
Early online date28 May 2022
DOIs
Publication statusPublished - Jun 2022

Scopus Subject Areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • biomarker
  • pyrrole-DNA adducts
  • pyrrole-protein adducts
  • pyrrolizidine alkaloids
  • retrorsine

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