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Cancer Letters Jun 1988Mouse leukemia cells (p388D1) were grown in medium containing various amounts of mitomycin C for 4 h. Cellular localization of protein B23 was detected using an...
Mouse leukemia cells (p388D1) were grown in medium containing various amounts of mitomycin C for 4 h. Cellular localization of protein B23 was detected using an immunofluorescence technique. Translocation of protein B23 from nucleoli to the nucleoplasm was observed with increasing dose of mitomycin C. To study the correlation of B23 translocation and drug resistance, three human colon carcinoma cell lines, HCT116, HCT116b (a line that is natively or intrinsically resistant to mitomycin C), and HCT116-44 (a line with an acquired resistance to mitomycin C), were employed. These cells were incubated with 1--150 micrograms/ml of mitomycin C. The drug concentration that caused 50% of the cells to have complete translocation (IC50) was determined for each cell line. The IC50 values of HCT116, HCT116b and HCT116-44 were 6, 10 and 50 micrograms/ml, respectively. These IC50 values correlate well with the mitomycin C resistant phenotype of these tumor cells as determined by other in vivo and in vitro assays (Willson, et al. (1985) Cancer Res., 45, 5281-5286). These results identify an inverse relationship between the ease of protein B23 translocation and the degree of mitomycin C resistance in human colon carcinoma cells. This relationship applies to cells that have either acquired mitomycin C resistance or intrinsic resistance to the drug.
Topics: Animals; Cell Nucleolus; Drug Resistance; Fluorescent Antibody Technique; Humans; Mice; Mitomycin; Mitomycins; Phosphoproteins; Tumor Cells, Cultured
PubMed: 3133107
DOI: 10.1016/0304-3835(88)90004-3 -
American Journal of Ophthalmology Feb 1994We treated three patients who had intraepithelial neoplasia involving the visual axis and a subsequent decrease of visual acuity with topical mitomycin C 0.02% four...
We treated three patients who had intraepithelial neoplasia involving the visual axis and a subsequent decrease of visual acuity with topical mitomycin C 0.02% four times daily for ten to 22 days. In two of the three cases, the intraepithelial neoplasia was histologically confirmed. The intraepithelial neoplastic lesion was replaced by biomicroscopically normal epithelium within nine weeks of the beginning of drug administration and did not recur during the four to 12 months of follow-up. Adverse reactions to topical mitomycin in two patients ranged from minimal conjunctival hyperemia after 14 days to marked hyperemia, ocular pain, and blepharospasm after 22 days. These signs and the symptoms, however, disappeared after the drug was discontinued. Administration of topical mitomycin C 0.02% for two weeks may be an effective treatment for corneal intraepithelial neoplasia that affects the visual axis.
Topics: Administration, Topical; Adult; Carcinoma in Situ; Corneal Diseases; Eye Neoplasms; Female; Humans; Male; Middle Aged; Mitomycin
PubMed: 8116744
DOI: 10.1016/s0002-9394(14)73072-7 -
Canadian Journal of Ophthalmology.... Oct 1997
Topics: Administration, Topical; Antibiotics, Antineoplastic; Cell Division; Eye Diseases; Fibroblasts; Humans; Intraoperative Period; Mitomycin; Ophthalmic Solutions; Postoperative Complications
PubMed: 9363339
DOI: No ID Found -
American Journal of Ophthalmology Sep 1993Because mitomycin C reduces the resistance to aqueous outflow normally provided by postoperative subconjunctival fibrosis, we would expect to see more frequent hypotony...
Because mitomycin C reduces the resistance to aqueous outflow normally provided by postoperative subconjunctival fibrosis, we would expect to see more frequent hypotony after trabeculectomy with mitomycin C than after standard trabeculectomy. To evaluate the incidence of hypotony in trabeculectomy with intraoperative mitomycin C use, we performed a retrospective analysis on 52 eyes of 48 patients who underwent trabeculectomy with mitomycin C. Mitomycin C concentration was 0.4 mg/ml in all eyes, and treatment time ranged from 3 1/2 to seven minutes. We defined hypotony as intraocular pressure lower than 5 mm Hg on two examinations at least four weeks apart and six weeks or more postoperatively. Overall, average intraocular pressure was 22.7 +/- 10.7 mm Hg preoperatively and 10.4 +/- 5.0 mm Hg postoperatively (P < .001), a mean reduction in intraocular pressure of 12.3 +/- 11.5 mm Hg (47.0%). Hypotony occurred in 17 of 52 eyes (32.7%). Seven eyes required trabeculectomy revision for hypotony. Hypotonous eyes received longer treatment with mitomycin C intraoperatively, with a mean application time of 5.3 +/- 1.0 minutes for hypotonous eyes and 4.7 +/- 0.8 minutes for nonhypotonous eyes (P = .03). Sixteen of 43 eyes (37.2%) undergoing primary filtration became hypotonous, as compared to one of nine (11.1%) eyes that had previous filtering procedures (chi 2 = 2.30, P = .13). Nine of 17 hypotonous eyes (52.7%) and five of 35 nonhypotonous eyes (14.3%) had loss of two or more lines of Snellen visual acuity. Hypotony occurred in nearly one third of eyes treated with mitomycin C during trabeculectomy in our study. There was a statistically significant (P = .03) association of hypotony with longer application time of mitomycin C, and a trend toward increased incidence of hypotony in primary filtration.
Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Glaucoma; Humans; Intraoperative Period; Male; Middle Aged; Mitomycin; Ocular Hypotension; Retrospective Studies; Trabeculectomy; Visual Acuity
PubMed: 8357056
DOI: 10.1016/s0002-9394(14)71349-2 -
American Journal of Ophthalmology May 1994
Topics: Chromatography, High Pressure Liquid; Glaucoma; Humans; Mitomycin; Sclera; Surgical Sponges; Trabeculectomy
PubMed: 8172278
DOI: 10.1016/s0002-9394(14)70079-0 -
Journal of Surgical Oncology Feb 1985In a four-year period, eight patients with mitomycin C extravasation ulcers were encountered. Mitomycin C extravasation produces a painful indolent ulcer that does not...
In a four-year period, eight patients with mitomycin C extravasation ulcers were encountered. Mitomycin C extravasation produces a painful indolent ulcer that does not have any tendency to heal. If extravasation of the drug is recognized, infusion should be stopped immediately, and the site of infusion should be changed. The ulcers should be excised, and primary closure is recommended; if it is not possible then the defect is covered by a partial thickness skin graft.
Topics: Extravasation of Diagnostic and Therapeutic Materials; Humans; Infusions, Parenteral; Mitomycin; Mitomycins; Necrosis; Skin Ulcer
PubMed: 3918215
DOI: 10.1002/jso.2930280207 -
Chemical Research in Toxicology Aug 2010Upon reduction, the antitumor drug mitomycin C undergoes a cascade of reactions to give a bis-electrophile that alkylates cellular nucleophiles. We recently reported...
Upon reduction, the antitumor drug mitomycin C undergoes a cascade of reactions to give a bis-electrophile that alkylates cellular nucleophiles. We recently reported that dithiols activate mitomycin C by reduction, and we report here that dithiols, after executing the reductive activation of mitomycin C, are bis-alkylated by the activated drug to form S,S'-cross-links as the predominant end products. The diastereomeric pair of adducts formed by 1,3-propanedithiol has been fully characterized by UV, HRMS, CD, and NMR experiments. Racemic dithiol (+/-)-dithiothreitol gave four diastereomeric cross-links, and (+/-)-dihydrolipoic acid gave eight cross-links (two regioisomers with four diastereomers each) that were partially characterized by UV and MS. The observed dependence of cross-link formation on dithiol concentration indicated the requirement of a second reduction step by dithiol, prior to the alkylation of the second arm of the dithiol. The existence of unidentified reaction pathways was manifested by the formation of unexpected intermediates during the course of the reaction of mitomycin C with dithiols and by the formation of unsoluble mitosene derivatives in the reaction between equimolar amounts of dithiol and mitomycin C. Mechanistic details of the reaction are addressed in light of these results. Finally, we discuss the potential relevance of our findings for the interaction of mitomycin C with dithiol-containing proteins.
Topics: Chromatography, High Pressure Liquid; Cross-Linking Reagents; Mass Spectrometry; Mitomycin; Molecular Conformation; Stereoisomerism; Sulfhydryl Compounds
PubMed: 20608688
DOI: 10.1021/tx100134h -
International Journal of Radiation... 1982The bioreductive alkylating agents are prodrugs for chemotherapy which are enzymatically reduced within cells to species capable of alkylating biological molecules and...
The bioreductive alkylating agents are prodrugs for chemotherapy which are enzymatically reduced within cells to species capable of alkylating biological molecules and producing cytotoxic damage. Studies presented in this report show that MIT-C has the characteristics expected of a bioreductive alkylating agent: activation to alkylating species occurs more readily under hypoxic conditions and the drug is selectively cytotoxic to hypoxic cells.
Topics: Alkylating Agents; Animals; Cell Survival; Cells, Cultured; Hydrogen-Ion Concentration; Hypoxia; Kinetics; Mitomycin; Mitomycins; Time Factors
PubMed: 6809706
DOI: 10.1016/0360-3016(82)90728-3 -
The Journal of Biological Chemistry Jul 2007Mitomycin C is a natural product with potent alkylating activity, and it is an important anticancer drug and antibiotic. mitN, one of three genes with high similarity to...
Mitomycin C is a natural product with potent alkylating activity, and it is an important anticancer drug and antibiotic. mitN, one of three genes with high similarity to methyltransferases, is located within the mitomycin biosynthetic gene cluster. An inframe deletion in mitN of the mitomycin biosynthetic pathway was generated in Streptomyces lavendulae to produce the DHS5373 mutant strain. Investigation of DHS5373 revealed continued production of mitomycin A and mitomycin C in addition to the accumulation of a new mitomycin analog, 9-epi-mitomycin C. The mitN gene was overexpressed in Escherichia coli, and the histidine-tagged protein (MitN) was purified to homogeneity. Reaction of 9-epi-mitomycin C with MitN in the presence of S-adenosylmethionine yielded mitomycin E showing that the enzyme functions as an aziridine N-methyltransferase. Likewise, MitN was also shown to convert mitomycin A to mitomycin F under the same reaction conditions. We conclude that MitN plays an important role in a parallel biosynthetic pathway leading to the subclass of mitomycins with 9alpha-stereochemistry but is not involved directly in the biosynthesis of mitomycins A and C.
Topics: Aziridines; Cations; Cloning, Molecular; Dose-Response Relationship, Drug; Escherichia coli; Gene Deletion; Histidine; Kinetics; Methyltransferases; Mitomycin; Mitomycins; Models, Chemical; Molecular Conformation; Streptomyces
PubMed: 17507379
DOI: 10.1074/jbc.M702456200 -
Revista Espanola de Fisiologia Dec 1987The effect of mitomycin C on the accumulation of specific mRNAs was studied in asynchronously growing Swiss 3T3 cells, as well as in synchronously growing serum...
The effect of mitomycin C on the accumulation of specific mRNAs was studied in asynchronously growing Swiss 3T3 cells, as well as in synchronously growing serum stimulated ts13 cells (a temperature-sensitive mutant from the BHK cell line). It was observed that the steady-state level of p53 RNA experienced some increase in 3T3 cells treated for 24 h with the drug. In addition, mitomycin when applied to serum stimulated ts13 cells increased the level of p2F1 RNA. Mitomycin diminished the level of core histone H3 RNA, a finding consistent with the inhibitory action of this compound on DNA replication.
Topics: Animals; Cell Cycle; Cell Line; DNA Replication; Gene Expression Regulation; Histones; Mice; Mitomycin; Mitomycins; RNA, Messenger; Transcription, Genetic
PubMed: 3129765
DOI: No ID Found