Toxic interaction between hydroxyurea and 1-beta-D-arabino-furanosylcytosine on the DNA of a human hepatoma cell line (HEPG2).
Hydroxyurea (HU) and 1-beta-D-arabino-furanosylcytosine (AraC) are two compounds used to inhibit DNA repair in the comet assay and thereby increase its sensitivity. We used RNA synthesis and comet assays to assess the cytotoxic and genotoxic effects of HU and AraC in the HepG2 cells after 1, 5, or 21 h of exposure to concentrations used to inhibit DNA repair. HU was genotoxic between 2 and 10 mM after 1 h of exposure and cytotoxic after 21 h. The presence of AraC (10, 50, or 100 microM) increased the DNA damage caused by HU (10 mM) suggesting a potentiation of the genotoxic effect. The interaction between the two inhibitors started after 5 h but was not dependent on the concentrations of AraC. Consequently, careful attention is required when employing a combination of HU and AraC, as their mechanisms of action could interfere with the interpretation of the data from genotoxicity assays.
UMR (1234), Toxicologie Alimentaire, INRA/ENSBANA 1, Esplanade Erasme, 21000 Dijon, France.
Isabelle
I
Severin
Martine
M
Padieu
Jean-Claude
JC
Lhuguenot
Marie-Christine
MC
Chagnon
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D020552:Comet Assay; D003561:Cytarabine / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004357:Drug Synergism; D006801:Humans; D006918:Hydroxyurea / Q000633:toxicity*; D008113:Liver Neoplasms / Q000473:pathology; D009153:Mutagens / Q000633:toxicity*
D009153:Mutagens; D003561:Cytarabine; D006918:Hydroxyurea