Effect of @entity13339 on DNA strand-break rejoining and XXXX in CHO cells treated with hydrogen peroxide.

@entity137 @entity274 @entity2145 @entity13339 @entity857 @entity3569
The influence of the nuclear @entity857 -ribosyltransferase inhibitor @entity13339 on the DNA strand-break rejoining kinetics and @entity137 in @entity3569 ovary cells following @entity274 treatment was investigated. For the DNA damage studies, cells were treated on ice with @entity274 (0-20 microM) for 1 h in serum-free medium, after which the @entity274 was removed and the cells were allowed to repair their damage in complete medium at 37 degrees C in the presence or absence of @entity13339 (5 mM) for periods up to 2 h. The DNA strand breaks remaining as a function of time were then estimated by alkaline elution. A linear relationship between the @entity274 concentration and the initial level of DNA single-strand breaks (zero time allowed for repair) was observed. No double-strand breaks or DNA-protein cross-links were detected at these doses. The rejoining of single-strand breaks after @entity274 (20 microM) alone was characterized by a single exponential process with a t1/2 of approx. 5 min. However, in the presence of @entity13339 , rejoining was much slower and biphasic, with t1/2 of approx. 10 and 36 min. The inhibitory action of @entity13339 was concentration-dependent and completely reversible in that, when the @entity13339 was removed from the treated cultures, the strand-break rejoining kinetics rapidly returned to the t1/2 of 5 min typical of @entity274 alone. Considerably higher concentrations of @entity274 (up to 600 microM) were required for cell killing compared to the DNA damage studies. Cell killing by @entity274 alone was characterized by a shoulderless, exponential survival curve (D0 = 880 microM). The @entity137 was potentiated when the cells were treated with @entity13339 (5 mM) for 1 h after the @entity274 treatment; the survival curve with @entity13339 also assumed a biphasic character (D0 of 212 microM and 520 microM). These results are consistent with the theory that @entity2145 .-induced single-strand breaks do not normally represent lethal lesions to the cell because of their rapid, efficient repair. However, interference with these repair processes (in this case by @entity13339 ) can alter this relationship, possibly allowing lesion fixation.
