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PubMed1981

Induction of Epstein-Barr virus early antigen, virus capsid antigen and virus DNA synthesis by mitomycin C.

The effect of mitomycin C was tested on Epstein-Barr virus (EBV) antigen and virus DNA synthesis in producer and non-producer cell lines. We found that producer, but not non-producer cell lines, are inducible for early antigen and virus capsid antigen synthesis. Although host DNA synthesis is effectively inhibited by over 99% in the presence of mitomycin C, virus DNA synthesis in the producer lines is unaffected and induced in parallel with the virus antigens.

Antigens, Viral↗
PubMed1990

Structure studies of mitomycins. III. Structure of M-83.

7-N-(p-Hydroxyphenyl)mitomycin C* (I), C21H22N4O6.H2O, Mr = 444.45, orthorhombic, P2(1)2(1)2(1), a = 8.056 (2), b = 33.832 (9), c = 7.469 (1) A, V = 2036 (1) A3, Z = 4, Dx = 1.45 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 8.8 cm-1, F(000) = 936, T = 293 K, R = 0.041 for 1923 observed reflections with F greater than 3 sigma (F). Although the overall structure, except the p-hydroxyphenyl group, is similar to mitomycin C, the bond lengths in the quinone ring are significantly influenced by the substituent. The phenyl and quinone rings are nearly planar and the two rings form a dihedral angle of 46.36 (7) degrees. Two quinone O atoms deviate from the least-squares planes of the quinone ring on the same side of the plane.

Animals↗
PubMed1989

Enhanced ATPase activity in liver cell nuclei induced by administration of mitomycin C to rats.

Intraperitoneal administration of mitomycin C (40 micrograms/100 g body weight) to male Wistar rats increased the ATPase activity in hypotonic extracts of liver cell nuclei for 4 days after injection. Partially purified ATPase, obtained by the DEAE-cellulose column chromatography of these extracts, showed a 14 times higher specific activity than that found in normal rat liver nuclei. The enzymatic activity was strongly enhanced by the addition of polynucleotides, especially poly A and poly I, to the assay mixture, but was inhibited by GTP, a chelating agent, heparin and thiol-group inhibitors. Quercetin and oligomycin were less effective, and ouabain showed no inhibitory effect. Mg2+ ions were essential, but neither Ca2+, Na+ nor K+ ions were required for the manifestation of the activity. These characteristic properties of the enzyme are similar to those of a nucleoside triphosphatase found in the nuclear matrix and envelope, suggesting that some energy-providing mechanisms involved in the repair processes of DNA damage or cellular injury are induced by mitomycin C administration.

Adenosine Diphosphate↗
PubMed1984

Two-step cell-death kinetics in vitro during cis-platinum, hydroxyurea and mitomycin incubation.

A human leukaemic cell line (REH) growing in suspension was incubated with cis-platinum, hydroxyurea and mitomycin C at various concentrations causing complete cell-cycle arrest. At different times the cell suspensions were harvested, diluted 1:1 with a buffer solution, stained without further treatment with a mixture of acridine orange (AO) and ethidium bromide (EB) and analysed with a biparametrical flow cytometer. Fluorescent plastic beads were introduced into the suspensions to provide an internal numerical reference for the control of cell loss. The fluorescence distributions showed three groups of cells: vital cells (V) which were only stained with AO; dead cells in which EB stained cytoplasmic components but not the nuclear DNA (D1), and dead cells which allowed EB to stain both cytoplasm and nuclear DNA (D2). The kinetics of cells entering D1 depended on drug concentration and showed equal characteristics for cis-platinum and mitomycin, but were different for hydroxyurea. The subsequent entry into D2 occurred about 15 hr later and showed no pronounced dependence on drug concentration. Parallel trypan-blue (TB) exclusion tests revealed that TB only stained D2 cells and therefore is not useful for investigating cell-death kinetics during exposure to cell-killing agents.

Antibiotics, Antineoplastic↗
PubMed1987

Veno-occlusive disease of the liver following chemotherapy with mitomycin C and doxorubicin.

A 54-year-old woman with metastatic breast cancer developed veno-occlusive disease of the liver following chemotherapy with mitomycin C and doxorubicin. The dose of mitomycin C received by this patient was much lower than that previously described to cause this complication. As both these drugs are used widely physicians should be aware of this complication.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Experimental intra-arterial infusion of Microencapsulated Mitomycin C into pelvic organs.

Laboratory experience with the use of Mitomycin C encased in ethylcellulose microcapsules as an agent for transcatheter embolisation is described. Microencapsulated Mitomycin C (MMC-m.c.) was infused into the pelvic organs of dogs by arterial catheterisation and the distribution of MMC in plasma and tissue was examined. MMC levels in the circulating blood of the MMC-m.c. group were significantly lower than those of the non-encapsulated MMC group. The biological potential of MMC was retained for prolonged periods in the pelvic organs after intra-arterial infusion of MMC-m.c. On the other hand, MMC could not be detected in the tissue of the non-encapsulated MMC group 4 h after the infusion.

Animals↗
PubMed1983

Intravesical instillation of mitomycin C in the prophylactic treatment of recurring superficial transitional cell carcinoma of the bladder.

Twenty-six patients with an elevated recurrence rate of stage O or A bladder tumours were treated prophylactically after transurethral resection (TUR) with short-term intravesical instillations of mitomycin C in a non-randomised study. The data before intravesical chemotherapy (IVC) were taken as the internal control for each patient. Mitomycin C was administered in one course of 10 daily doses of 40 mg, starting 24 to 48 hours after TUR. The average follow-up was 13.9 months before and 28.5 months after IVC. Before IVC, the average number of recurrences was 2.6, with an average recurrence rate of 1 every 5.3 months. After IVC there was no tumour recurrence in 4 patients, with a mean of 12.2 months' follow-up, but there was tumour recurrence in 22 patients. For 17 patients (77%) the free interval averaged 2.3 times longer than the mean interval of recurrence before IVC and for 18 patients (82%) the recurrence rate averaged 3.3 times less than the recurrence rate before IVC.

Aged↗
PubMed1985

Mitomycin C in superficial bladder cancer: 24-month follow-up.

Twenty-three patients who were given intravesical Mitomycin C for treatment of superficial bladder cancer have been followed up for a further 12 and 24 months after an initial assessment 5 weeks after completing therapy. At 5 weeks 17 (74%) showed complete disappearance of tumour and 4 (17%) showed a partial response. Twelve months later 8 (35%) remained tumour-free and 15 (65%) had recurrences; 5 of these (22% of all patients) had progressed to invasive cancer. The results at 24 months were little different except that one further patient (27% in all) progressed to invasive cancer. Six patients with symptomatic carcinoma in situ became symptom-free after Mitomycin C, but despite remaining free of symptoms three have progressed to invasive cancer. This small series shows that involvement of large areas of bladder urothelium by tumour, carcinoma in situ and previous therapy for tumour are unfavourable prognostic indices.

Antibiotics, Antineoplastic↗
PubMed1990

Reduced bladder capacity in patients receiving intravesical chemoprophylaxis with mitomycin C.

After complete resection of superficial bladder carcinoma (Tis-2, G1-3), 75 patients were treated prophylactically with either 20 or 30 mg mitomycin C. Six patients developed a substantial reduction in bladder capacity (less than 200 ml). In 2 patients radical cystectomy of an otherwise tumour-free fibrotic bladder was necessary. The results of long-term treatment (2 years) suggest that reduced bladder capacity correlates with the cumulative dosage of mitomycin C.

Administration, Intravesical↗
PubMed1989

No difference between smoking lung cancer patients and smoking controls in the frequency of spontaneous and mitomycin C induced chromosome aberrations in lymphocytes.

Lymphocytes from 21 male smokers, 10 untreated lung cancer patients, and 11 controls were cultured with and without exposure to mitomycin C. There were no differences between the chromosome aberration frequencies in the two groups: the spontaneous aberration frequency was 8.5% among patients and 8.4% among controls, whereas after mitomycin C induction the corresponding frequencies were 25.5% and 24.6%, respectively.

Aged↗
PubMed1985

Enhanced delivery of mitomycin C derivatives through hairless mouse and rat skins.

The percutaneous permeation characteristics of two lipophilic mitomycin C derivatives with aromatic moieties were determined using excised hairless mouse and rat skins and compared with those of mitomycin C (MMC). 1a-N-Benzylmitomycin C penetrated more readily through both kinds of skin than MMC without metabolic conversion. 1a-N-Benzyloxycarbonylmitomycin C effected a 4-fold increase in the delivery of MMC through the rat skin and was completely converted to MMC by an enzyme in rat skin. However, saturation of the metabolic conversion activity was observed in the hairless mouse skin.

Administration, Topical↗
PubMed1964

PHENETHYL ALCOHOL SYNERGISM WITH MITOMYCIN C, PORFIROMYCIN, AND STREPTONIGRIN.

Cyanide and phenethyl alcohol greatly enhance the lethal action of mitomycin C, porfiromycin, and streptonigrin on an exponentially growing culture of Escherichia coli. Dinitrophenol similarly enhances the lethal action of mitomycin C and porfiromycin, but only slightly that of streptonigrin. Phenethyl alcohol may be functioning in these experiments as an inhibitor of electron transport.

Alcohols↗
PubMed1981

Characterization of Salmonella toxin released by mitomycin C-treated cells.

The enzyme-linked immunosorbent assay and the Chinese hamster ovary floating cell assay for cholera toxin have proven to be sensitive and reliable tests for determining the antigenic and biological characteristics of Salmonella toxin, respectively. The addition of mitomycin C to the culture media 3 h after inoculation resulted in increased amounts of Salmonella toxin in culture filtrates but had the reverse effect on cell sonic extracts. Our data suggested that the increased amounts of Salmonella toxin culture filtrates caused by mitomycin C were due to cell lysis, resulting in the release of intracellular toxin, rather than to an increase in the synthesis of Salmonella toxin. The biological activity of Salmonella toxin was heat labile at 100 degrees C. The antigenic structure of the toxin appeared to remain intact after exposure to temperatures as high as 100 degrees C but was altered somewhat when the toxin was subjected to autoclaving. The toxin had an isoelectric point in the pH range from 4.3 to 4.8 and an estimated molecular weight which appeared to be more than 110,000. With the exception of the range for its isoelectric point, its molecular weight, and its low concentration in filtrates and sonic extracts, Salmonella toxin was very similar in biological and antigenic characteristics to cholera toxin. The antigenic and biological assays described here provide an effective basis for extending our study of Salmonella toxin.

Animals↗
PubMed1988

Use of a simian virus 40-based shuttle vector to analyze enhanced mutagenesis in mitomycin C-treated monkey cells.

When monkey cells were treated with mitomycin C 24 h before transfection with UV-irradiated pZ189 (a simian virus 40-based shuttle vector), there was a twofold increase in the frequency of mutations in the supF gene of the vector. These results suggest the existence of an enhancible mutagenesis pathway in mammalian cells. However, DNA sequence analysis of the SupF- mutants suggested no dramatic changes in the mechanisms of mutagenesis due to mitomycin C treatment of the cells.

Animals↗
PubMed1983

Haemolytic-uraemic syndrome complicating long-term mitomycin C and 5-fluorouracil therapy for gastric carcinoma.

Three cases of acute renal toxicity in patients receiving long-term therapy with mitomycin C and 5-fluorouracil are reported. Two of the patients (1 and 3) are from a multicentre trial of adjuvant chemotherapy for gastric carcinoma. All three cases showed extensive fibrin deposition in the kidneys and lungs, the appearances of the renal lesions being similar to those seen in the haemolytic-uraemic syndrome. Two of the three cases had received blood transfusions, and attention is drawn to the possibility that mitomycin C may sensitise the kidneys to minor mismatches. With the increasing use of these antimitotic agents, great vigilance should be exercised with regard to renal function and haemolytic status.

Adult↗
PubMed1984

Arterial chemoembolization of hepatocellular carcinoma with mitomycin C microcapsules.

Chemoembolization by selective intra-arterial infusion of mitomycin C in microcapsule form exerts potential therapeutic effects through infarction and prolonged activity. Of 20 patients with inoperable hepatocellular carcinoma (HCC) treated with one or more courses via a hepatic arterial catheter, a change in tumor size could be measured in 16. Measurable tumor regression amounting to greater than 50% was shown in 6 patients (38%), 25-50% in 3 (19%), and less than or equal to 25% in 6 (38%), while tumor increased in 1. Serum alpha-fetoprotein, which was greater than 300 ng/ml before treatment in 13 patients, clearly fell after treatment in 10 (77%). The survival rate at 3, 6, and 12 months after treatment was 75%, 65%, and 24%, respectively, for all patients, and 92%, 85%, and 38% in 11 patients without a tumor cast in the portal vein or its major branches. Systemic toxicity was mild, and all patients tolerated treatment well. These results indicate that chemoembolization with mitomycin C microcapsules is a useful palliative measure for treatment of inoperable HCC.

Adult↗
PubMed1985

[Significance of urothelial dysplasia in macroscopically normal mucosa in patients with bladder tumors. Results of a randomized study with and without intravesical mitomycin C in the prevention of recurrence].

During endoscopic treatment of 90 patients with bladder tumors, multiple random biopsies were carried out on normal looking bladder mucosa. Dysplasias were found in 25.6% of the patients. These findings are almost identical to the results of histological examination of bladder in autopsies. Postoperatively, a randomized prophylactic Mitomycin instillation therapy was carried out. Although the recurrence rate under Mitomycin treatment was significantly lower here than in the control group (18.8% vs. 56.7%), the rate of dysplasias was nearly twice as high as in the control group (43.8% vs. 23.3%). Therefore, the conclusion can be drawn that dysplasia only reflects the present picture of proliferative activity of urothelium, but allows no interpretation of biological activity or prognosis of bladder carcinoma.

Aged↗
PubMed1983

Mitomycin C in patients with metastatic breast cancer refractory to hormone therapy and chemotherapy.

43 patients with advanced breast cancer, resistant to conventional therapies, were treated with mitomycin C at a dose of 20 mg/m2 i.v. every 6 weeks. No response was observed. The most common side effect was myelotoxicity. Leukopenia occurred in 63% of the patients, thrombocytopenia in 67%, and anemia in 14%. Two episodes of acute dyspnea were observed which were thought to be pulmonary hypersensitivity reactions. This study does not suggest that mitomycin C is of value as second- or third-line treatment in metastatic breast cancer. It is likely that the drug could play a more important role in combination with other chemotherapeutic agents.

Adult↗