Cellular Mitomycin

Mitomycin C was found to have broad activity against a range of tumors and has been used clinically since the early 1960s [14, 15]. It causes many specific cellular effects, including inhibition of DNA synthesis, recombination, chromosome breakage, sister chromatid exchange, induction of DNA repair, and induction of... 

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. 

Imray FP, Smith PJ, Relf W et al. Wilms tumour association with cellular sensitivity to mitomycin C in patients and first-degree relatives. Lancet 1984 1 1148-1151. 

We evaluated delayed hypersensitivity to examine the participation of CVS administration on the cellular immunity to Meth A tumor antigens according to the delayed footpad reaction (DFR) [48] in the tumor i.v. rechallenge system. On day 9, 16, or 23, a quantity of 5 x 10 mitomycin C-treated Meth A cells in 0.05 ml PBS were injected into the right hind footpad of each BALB/c mouse. PBS injected into the left hind footpad... 

The antibiotic mitomycin C, introduced to give a concentration of 10 jLtg. per ml. in the perfusing blood at the outset, and a continuous infusion of a total of 1 mg. over the course of 4 to 5 hours, was also associated with significant suppression of fibrinogen biosynthesis. The concentrations of mitomycin C used here are at least ten times that which significantly inhibited cellular multiplication in isolated cell cultures. Further studies at lower concentration levels with both puromy-cin and mitomycin C are indicated. 

There are other examples of the influence of PolyPs on the expression of some genes omitting rpoS. If the level of cellular PolyP in E. coli was reduced to a barely detectable concentration by overproduction of exopolyphosphatase (Shiba et al., 1997), the cells were more sensitive to UV or mitomycin C than the control cells. PolyP accumulation was observed after treatment with mitomycin C, whereas the PolyP level was below the detectable level... 

Figure 3. Mitomycin C induced thrombotic microangiopathy. Glomeruli show swelling and detatchment of endothelial cells and luminal occlusion. The arterioles and arteries show intimal cellular swelling and hyperplasia and fibrin deposition. Masson s trichrome staining, magn. x325.

Matsumoto, S., Yamamoto, A., Takakura, Y., Hashida, M. and Sezaki, H. (1986) Cellular interaction and in vitro antitumour activity of mitomycin C-dextran conjugate. Cancer Res. 46 4463-4468. 

Bleomycin causes cellular DNA damage by an oxidative mechanism adriamycin and daunomycin also produce oxidative damage as part of their repertoire of reactions in cells. Other quinone antitumor drugs used in the clinic, including mitomycin C, mitroxanthone, and mithramycin, may also require cellular iron to catalyze formation of reactive oxidants. Thus, quite apart from... 

A number of other antibiotics in addition to chloramphenicol and puromycin have been examined to determine their action upon actinomycin and protein synthesis as well as the size of the intracellular amino acid pool (Katz and Weiss-BACH, 1962, 1963 Katz, Wise and Weissbach, 1965). Streptomycin, neomycin, tetracycline, and erythromycin, which have been shown in other systems to inhibit protein synthesis, have all been found to stimulate actinomycin synthesis (Table 12). In each case incorporation of C-label into cellular proteins of 5. anti-hioticus was inhibited extensively whereas the C-labeled pool was larger in the presence of the antibiotics. Vancomycin and penicillin, inhibitors of cell wall synthesis, and actinomycin, which has been shown to inhibit the DNA dependent RNA S5mthesis, had no influence on actinomycin synthesis by this organism. The addition of mitomycin also had no effect on antibiotic formation. 

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