Neoplasma Vol.51, p.442-449, 2004
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Title: Effect of cytosine arabinoside and hydroxyurea on micronucleus
formation induced by model clastogens in Chinese hamster V79 cells
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Author: Z., VALOVICOVA
; A., GABELOVA
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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.
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Keywords: micronucleus assay, cytosine arabinoside, hydroxyurea, N-methyl-N-
nitroso urea, UV-light, Chinese hamster V79 cells
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Year: 2004, Volume: 51, Issue: |
Page From: 442, Page To: 449 |
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