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Mitomycin C. (mitomycin + c)
Selected AbstractsLimited concentration of RecA delays DNA double-strand break repair in Deinococcus radiodurans R1MOLECULAR MICROBIOLOGY, Issue 1 2006Edmond Jolivet Summary To evaluate the importance of RecA in DNA double-strand break (DSB) repair, we examined the effect of low and high RecA concentrations such as 2500 and 100 000 molecules per cell expressed from the inducible Pspac promoter in Deinococcus radiodurans in absence or in presence of IPTG respectively. We showed that at low concentration, RecA has a negligible effect on cell survival after ,-irradiation when bacteria were immediately plated on TGY agar whereas it significantly decreased the survival to ,-irradiation of ,ddrA cells while overexpression of RecA can partially compensate the loss of DdrA protein. In contrast, when cells expressing limited concentration of RecA were allowed to recover in TGY2X liquid medium, they showed a delay in mending DSB, failed to reinitiate DNA replication and were committed to die during incubation. A deletion of irrE resulted in sensitivity to ,-irradiation and mitomycin C treatment. Interestingly, constitutive high expression of RecA compensates partially the ,irrE sensitization to mitomycin C. The cells with low RecA content also failed to cleave LexA after DNA damage. However, neither a deletion of the lexA gene nor the expression of a non-cleavable LexA(Ind,) mutant protein had an effect on survival or kinetics of DNA DSB repair compared with their lexA+ counterparts in recA+ as well as in bacteria expressing limiting concentration of RecA, suggesting an absence of relationship between the absence of LexA cleavage and the loss of viability or the delay in the kinetics of DSB repair. Thus, LexA protein seems to play no major role in the recovery processes after ,-irradiation in D. radiodurans. [source] Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1)BJU INTERNATIONAL, Issue 3 2001M.C. Hayes Objective To compare multidrug resistance (MDR)-1 and MDR-3 gene expression in a new urothelial cancer cell line (MGHU-1, with resistance to mitomycin C) against controls and the established (epirubicin-resistant) MDR clone, and to correlate MDR with cytotoxicity data. Materials and methods Resistance to mitomycin C was induced by the long-term exposure of wild-type MGHU-1 cells to increasing concentrations (20,400 nmol/L) of mitomycin C. The cytotoxicity of mitomycin C or epirubicin was then compared in MGHU-1, MGHU-MMC (mitomycin C-resistant) and MGHU-1R (established MDR) cells, using the tetrazolium biomass assay. The expression of MDR-1 and -3 was investigated by the reverse transcriptase-polymerase chain reaction, using cDNA-specific primers after titration, and compared with DNA and negative controls. Results MDR-1 and -3 were significantly and equally overexpressed in MGHU-1R, and associated with a dramatic increase in the 50% inhibitory drug concentration (P < 0.001) for mitomycin C and epirubicin against controls. In MGHU-MMC, the overexpression of MDR-1 was three times greater than that of MDR-3. The cytotoxicity profile for both agents was very similar to that of MGHU-1R. Trace amounts of MDR-1, but not MDR-3, were identified in the MGHU-1 wild-type. Conclusions Urothelial cancer cell resistance to mitomycin C is associated with cross-resistance to epirubicin and overexpression of MDR-1, suggesting that mitomycin C falls within the MDR category. Clinical application of this methodology may allow patients to be identified who are unlikely to benefit from intravesical chemotherapy. [source] Impaired removal of DNA interstrand cross-link in Nijmegen breakage syndrome and Fanconi anemia, but not in BRCA-defective groupCANCER SCIENCE, Issue 11 2008Ken Tsuchida Human diseases characterized by a high sensitivity to DNA interstrand cross-links (ICL) and predisposition to malignance include Nijmegen breakage syndrome (NBS) and Fanconi anemia (FA), which is further classified to three groups: (1) FA core-complex group; (2) FA-ID complex group; and (3) breast cancer (BRCA)-defective group. The relationships between these four groups and the basic defect in ICL repair remain unclear. To study the details of ICL repair in NBS and FA, a highly sensitive PPB (psoralen,polyethylene oxide,biotin) dot blot assay was developed to provide sensitive quantitative measurements of ICL during the removal process. Studies utilizing this assay demonstrated a decreased rate of ICL removal in cells belonging to the FA core-complex group (e.g. groups A and G) and FA-ID complex group (group D2), while ICL removal was restored to normal levels after these cells were complemented with wt-FANCA, wt-FANCG and wt-FANCD2. Conversely, FA-D1 cells with a defective BRCA2 protein displayed normal ICL removal, although they were compromised with respect to recombination. This normal ICL removal rate in recombination-deficient cells was confirmed by using XRCC3-defective Chinese hamster cells, which are similarly compromised with respect to recombination and are sensitive to mitomycin C. The present study also showed that cells from patients with Nijmegen breakage syndrome were defective in ICL removal, while they were impaired in the recombination. These results indicate an obvious defect of FA and NBS in the ICL repair process, except in the BRCA-defective group, and a separate step of recombination-mediated repair pathway between the BRCA group and NBS. (Cancer Sci 2008; 99: 2238,2243) [source] Corneal and conjunctival findings after mitomycin C application in pterygium surgery: an in-vivo confocal microscopy studyACTA OPHTHALMOLOGICA, Issue 2 2009Andrey Zhivov Abstract. Purpose:, To perform a qualitative assessment of the topical side-effects of mitomycin C on cornea after pterygium surgery. Methods:,In-vivo confocal microscopy (Heidelberg Retina Tomograph II in combination with the Rostock Cornea Module) was performed in 10 patients with unilateral primary pterygium. Mitomycin C 0.02% was applied topically to seven eyes for 5 min intraoperatively and twice daily for 5 days postoperatively. Three eyes underwent surgery without application of cytostatic agent. Patient follow-up was 1 month. Results:, After application of mitomycin C, complete epithelialization of the operated zone was found 2 weeks after surgery. In-vivo confocal microscopy revealed signs of superficial punctate keratitis for 2 weeks in the central cornea only after application of mitomycin C. The presence of epithelial and stromal oedema in this group was noted for up to 2 weeks in the central cornea and for up to 4 weeks in the operated zone. In the control group, complete epithelialization was found after 1 week; there were no signs of oedema after 1 week in the central cornea or after 2 weeks in the operated zone. Leucocyte infiltration and increased Langerhans cell density were noted in both groups in the operated and central zones. Analysis of the conjunctiva revealed a decrease in goblet cell density following cytostatic application. Conclusion:, Local application of mitomycin C delays corneal epithelialization, and prolongs postoperative epithelial and stromal oedema in both the centre and periphery. Moreover, signs of punctate keratitis were noted 2 weeks after surgery in central intact cornea. Nevertheless, in-vivo confocal microscopy shows that these changes are reversible 4 weeks after application of mitomycin C 0.02%. [source] | ||||||||||