Shiga toxin 1 and ricin inhibit the repair of H2O2-induced DNA single strand breaks in cultured mammalian cells.
A growing body of evidence suggests that ribosome-inactivating proteins (RIPs) remove adenine moieties not only from rRNA, but also from DNA--an effect leading to DNA damage in cultured cells. We herein report that two distinct RIPs of bacterial (shiga toxin 1, Stx1) and plant (ricin) origin, inhibit the repair of the DNA lesions generated by hydrogen peroxide in cultured human cells. This effect is unrelated either to inhibition of protein synthesis or to depletion of cellular antioxidant defenses and is likely to derive from direct interactions with cellular DNA repair machinery. Therefore, the genotoxicity of these toxins on mammalian cells seems to be a complex phenomenon resulting from the balance between direct (DNA damaging activity), indirect (DNA repair inhibition) effects and the eventual presence of other DNA damaging species. In particular, with regard to Stx1, it could be hypothesized that Stx-producing bacteria increase the risk of transformation of surrounding, inflamed tissues in the course of human infections.
Sestili
Piero
P
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo", Via S. Chiara 27, 61029 Urbino (PU), Italy. sestili@uniurb.it
Alfieri
Roberta
R
Carnicelli
Domenica
D
Martinelli
Chiara
C
Barbieri
Luigi
L
Stirpe
Fiorenzo
F
Bonelli
Mara
M
Petronini
Pier Giorgio
PG
Brigotti
Maurizio
M
D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012276:Ricin / Q000009:adverse effects*; D022622:Shiga Toxin 1 / Q000009:adverse effects*
D016877:Oxidants; D022622:Shiga Toxin 1; D004247:DNA; D012276:Ricin; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase