title: Effect of cytosine arabinoside and hydroxyurea on micronucleus formation induced by model clastogens in Chinese hamster V79 cells.
abstract: Post-cultivation of treated cells in the presence of DNA repair inhibitors has been proposed as a new methodological approach of the micronucleus (MN) assay to increase the sensitivity of this technique. In order to assess the advantages and limitations of this promising methodological approach, several genotoxic/clastogenic agents with different mechanisms of activity were chosen to assess the effect of DNA repair inhibitors on the level of micronuclei (MNi) induced by particular agent using Chinese hamster V79 cells. Both UV light (UV) and benzo(a)pyrene (BaP) increased significantly the micronucleus level in V79 cells (p<0.01-0.001). In contrast, only at cytotoxic concentration (>0.8 mM) a slight but statistically significant rise of MNi was determined in cells exposed to N-methyl-N-nitroso urea (MNU). However, post-cultivation of MNU-treated cells in the presence of DNA repair inhibitors (cytosine arabinoside, AraC and hydroxyurea, HU) led to an additional rise of MNi. While AraC had a synergistic effect on MN formation (0.4 mM and 0.8 mM, DS=2.14 and 1.13, respectively), HU had less than additive effect (DS=0.86 and 0.66) and the combined treatment of cells with AraC and HU was least effective (Cf=0.36 and 0.28). On the other hand, post-cultivation of UV- and BaP-treated cells in the presence of AraC did not result in any synergistic effect on MN formation. No effect or even a decrease of MNi was measured particularly due to HU or combined treatment of HU and AraC. Incubation of control untreated cells with AraC gave rise to a significant increase of MN formation (2- to 2.5-fold) as well. Hydroxyurea or the combined treatment of HU with AraC had lower effect on the spontaneous level of MNi. Our study shows, that the combination of MNU treatment with DNA repair inhibitors increased the number of MNi on well proliferating V79 cells; in case UV light and BaP treatment, the involvement of DNA repair inhibitors did not contribute to an increase of sensitivity of MN assay. On the basis of our results we suppose that the AraC/CBMN assay might be a promising approach in genetic toxicology applied only to lymphocytes.
authors.affiliation: Cancer Research Institute of Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. zuzana.valovicova@savba.sk
authors.forename: Z
authors.initials: Z
authors.lastname: Valovicová
authors.forename: A
authors.initials: A
authors.lastname: Gábelová
mesh_terms: D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D003561:Cytarabine / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens
chemical_list: D009153:Mutagens; D003561:Cytarabine; D006918:Hydroxyurea