Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MITOMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1982

Generation of hydroxyl radical by anticancer quinone drugs, carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, in the presence of NADPH-cytochrome P-450 reductase.

The generation of hydroxyl free radicals in the system consisting of purified NADPH-cytochrome P-450 reductase and anticancer quinone drugs, such as carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, has been confirmed by two methods. In the spin trapping study, using N-tert-butyl-alpha-phenylnitrone as the spin trapping agent, four drugs generated hydroxyl radical-trapped signals, and the formation of the spin adduct was dependent on time and the enzyme concentration. Among the four drugs, the generation time of signal was in the order of carbazilquinone, aclacinomycin A, adriamycin and mitomycin C, but the magnitude of signal intensity was different. In both aclacinomycin A and adriamycin, the signal disappeared in a few minutes. Catalase completely inhibited the formation of the spin adduct, while superoxide dismutase did not significantly inhibit, but effected in some manner. The generation of hydroxyl radical was also confirmed by the ethylene production from methional. Among the four drugs, the order of the magnitude of ethylene production was different from that of signal intensity by ESR study. Catalase potently inhibited the ethylene production, while superoxide dismutase effected in some manner. From these results, the interactions of anticancer quinone drugs with NADPH-cytochrome P-450 reductase and oxygen, and the possible relations of the enzymes to the radical related actions of these drugs are discussed.

Aclarubicin↗
PubMed1984

Mitomycin C-induced deoxyribose degradation inhibited by superoxide dismutase. A reaction involving iron, hydroxyl and semiquinone radicals.

Mitomycin C stimulates deoxyribose degradation with the release of thiobarbituric acid-reactive material under conditions of low oxygen concentration. This damage is inhibited by scavengers of the hydroxyl radical, iron chelators and the specific proteins catalase and superoxide dismutase. The reactive radical species appears to arise from a Fenton-type sequence in which iron is reduced by the mitomycin C semiquinone radical.

Animals↗
PubMed1988

Mitomycin C-treated 3T3/B (3T3/A31) cell feeder layers in hybridoma technology.

Several methods were compared for their efficiency at supporting the growth of hybridoma cells at low cell densities. Soluble growth factors from different sources gave poor results, whereas actively metabolising syngeneic cells proved to be effective feeder systems. Of the latter, the transformed subline of BALB/c embryo fibroblast 3T3/B cells - 3T3/A31 - were best. Macrophage (peritoneal exudate) feeder layers could be as effective as the 3T3/A31 cells, but were much more variable, probably reflecting the physiological state of the donor mice, the degree of sensitisation of the cells in vitro and the rate of recovery after isolation from the peritoneal cavity. Since the 3T3/A31 cells could replicate more rapidly than the hybridoma cells, division of the feeder cell chromosomes was inhibited using mitomycin C; 1-2 X 10(4) 3T3/A31 cells/ml were treated with 1 microgram/ml mitomycin C for 8-16 h at 37 degrees C, washed, and incubated for 3-7 days at 37 degrees C. The latter incubation was to permit the metabolism and breakdown of unreacted but intracytoplasmic drug, and the establishment of an active feeder layer before use with the hybridoma cells.

Animals↗
PubMed1984

Exposure to low concentrations of mutagens alters the mutagenic and lethal effects of 4-nitroquinoline-N-oxide and mitomycin C in Escherichia coli.

Mitomycin C and 4-nitroquinoline-N-oxide are two mutagens which can induce the SOS DNA repair system in Escherichia coli. Growth of E. coli B/r strain WP2, or its uvrA- derivative, in very low concentrations of either mutagen led to the increased sensitization to the lethal and/or mutagenic effects of a subsequent challenge with the same mutagen. These phenomena were not observed in either the recA- or lexA- derivatives of the parent strain. Induction of the adaptive response repair pathway by prior cultivation in low concentrations of N-methyl-N'-nitro-N-nitrosoguanidine reduced both the mutagenic and lethal effects of a subsequent challenge with mitomycin C but not 4-nitroquinoline-N-oxide.

4-Nitroquinoline-1-oxide↗
PubMed1986

Spontaneous and induced chromosomal aberrations and gene mutations in human lymphoblasts: mitomycin C, methylnitrosourea, and ethylnitrosourea.

The concentration-dependent mutagenic, clastogenic, and cytocidal activities of mitomycin C (MC), methylnitrosourea (MNU), and ethylnitrosourea (ENU) were measured in the human lymphoblast cell line TK6. For treatments resulting in fewer than 2 lethal hits, MNU, ENU, and MC gave rise to apparently linear dose-response curves for gene mutations (hgprt and tk genes) as well as for chromosomal aberrations. The numbers of induced mutants at the tk and hgprt loci were similar between the two loci for each compound. However, the ratio of mutagenic activity relative to the clastogenic activity (aberrations/cell) was lowest for mitomycin C, intermediate for methylnitrosourea, and highest for ethylnitrosourea. These results confirm in human cells the general observation that the processes of mutagenesis and clastogenesis are nonidentical: compounds vary independently in their mutagenic and clastogenic potentials.

Cell Line↗
PubMed1990

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer.

Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (BOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a second-line chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.

Adult↗
PubMed1991

A phase II evaluation of cisplatin, bleomycin, and mitomycin-C in patients with recurrent squamous cell carcinoma of the cervix.

Cisplatin, bleomycin, and mitomycin-C were used to treat 25 patients with recurrent squamous cell carcinoma of the cervix. Six patients had a partial response, yielding a total response rate of 27%. Nine patients had stable disease. The median survival for the whole group was 30 weeks. The median survival for responders was 32 weeks. The median progression free interval for the whole group was 12 weeks and the median progression-free free interval for responders was 14 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, bleomycin, and mitomycin-C has modest effectiveness in the treatment of recurrent squamous cell carcinoma of the cervix, but represents no improvement over single-agent chemotherapy.

Adult↗
PubMed1991

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗
PubMed1989

Hypersensitivity to mitomycin C cell-killing in Roberts syndrome fibroblasts with, but not without, the heterochromatin abnormality.

Roberts syndrome (RS) is a rare genetic disorder, characterized clinically by severe pre- and post-natal growth retardation and symmetric limb reduction deformities. Some patients with RS have a distinctive abnormality of the constitutive heterochromatin (the RS effect) which has been described as a premature separation of the paracentromeric and nucleolar organizing regions of the chromosomes and the distal portion of the long arm of the Y chromosome (German, 1979). These patients [denoted RS(+)] are clinically indistinguishable from the RS(-) patients who lack the cytogenetic marker for Roberts syndrome. Recently, a mutant in Drosophila has been described which has both heterochromatin undercondensation and hypersensitivity to mutagen treatment (Gatti et al., 1983). The authors suggested that the uncondensed heterochromatin may be more accessible to damage by mutagens. Thus, the present study was an investigation of the mutagen sensitivity in Roberts syndrome, to determine whether there is a similar relationship between abnormal heterochromatin structure and mutagen sensitivity. Plating efficiency experiments were performed with RS(+) fibroblasts, RS(-) fibroblasts, RS heterozygous fibroblasts and a large assortment of appropriate control cells. The RS fibroblasts with the heterochromatin abnormality were consistently more sensitive (based on D10 values) to mitomycin C treatment than were any of the other cell strains tested, including RS(-) cells. These results support the hypothesis that mitomycin C sensitivity and abnormal heterochromatin structure in Roberts syndrome are related.

Abnormalities, Multiple↗
PubMed1991

Kinetochore analysis of micronuclei allows insights into the actions of colcemid and mitomycin C.

We have induced micronuclei in two strains of diploid human fibroblasts with a known aneugen, colcemid, and a known clastogen, mitomycin C. Using immunofluorescence to detect the presence of kinetochores in micronuclei, we were able to demonstrate a 26.8-fold increase in fluorescence-positive micronuclei (aneuploidy) in colcemid-treated cells. However, colcemid also induced an increase in kinetochore-negative micronuclei. Our findings support previous reports that suggest colcemid may induce chromosome breakage in addition to its major aneugenic effect. The frequency of kinetochore-negative micronuclei (chromosome breakage) in mitomycin C-treated cells rose an average of 7.9-fold in the two test strains, a clear reflection of its clastogenic action. However, a 4-fold increase in the kinetochore-positive fraction was seen. We conclude that the fibroblast micronucleus assay, coupled with kinetochore immunofluorescence, provides a useful screening approach for genotoxic agents. The delineation of the precise mechanism by which an agent perturbs the rates of chromosomal breakage or lag may require more detailed analysis.

Aneuploidy↗
PubMed1982

Comparative studies on spontaneous and mitomycin-C-induced sister-chromatid exchanges in smokers and non-smokers.

Both spontaneous and mitomycin-C-induced sister-chromatid exchanges were analyzed in 6 smokers and 6 non-smokers. The average number of spontaneous SCE in smokers' cells was 8.33 +/- 1.08. The frequency in the non-smoking controls was 4.41 +/- 0.72. This difference is highly significant (P less than 0.001). Smokers also had more SCE at all levels of mitomycin C testes. Analysis of variance showed these differences to be highly significant (P less than 0.001).

Cells, Cultured↗
PubMed1989

Inhibition of mitomycin C-induced sister-chromatid exchanges in mouse bone marrow cells by the immunopotentiators Krestin and Lentinan.

We have carried out an investigation to determine whether or not the sister-chromatid exchange frequencies (SCEs) observed in bone marrow cells in mice treated with mitomycin C (MMC) are inhibited by the immunopotentiators Krestin and Lentinan. We found that mitomycin C (2 mg/kg, i.v.)-induced SCEs were inhibited in 27% of the mice treated with Krestin (300 mg/kg, i.p.) and in 23% of the mice treated with Lentinan (1 mg/kg, i.p.). The effects of Krestin were found to be dose-dependent in inhibition of MMC-induced SCEs while those of Lentinan were not. Our findings therefore suggest that Krestin and Lentinan are not only useful for cancer treatment as immunopotentiators in combination with anticancer drugs but may also prevent the increase of chromosomal damage induced by anticancer drugs.

Adjuvants, Immunologic↗
PubMed1989

Sister-chromatid exchanges induced by mitomycin C after acute or chronic exposure of human lymphocytes to a low dose of X-rays.

Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays. Acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycin C-induced sister-chromatid exchange aberrations. The effect was small (approximately 10%) with evidence of some variability between donors. By contrast no adaptive response was observed if the cells were treated in G0.

Adaptation, Physiological↗
PubMed1989

Chromosomal hypersensitivity in mutant MCN-151 mouse cells exposed to mitomycin C.

After exposure to mitomycin C, the mouse lymphoma cell mutant MCN-151, previously shown to be sensitive to the toxic effect of the drug, demonstrates higher frequencies of chromatid-type aberrations and of aberrant cells in comparison to L5178Y cells. At any given dose of mitomycin C, the frequencies of chromosomal aberrations increased with time reaching a plateau in both cell strains, with the mutant in all cases being more sensitive than normal cells.

Animals↗
PubMedDate not supplied

Sensitivity of Bloom syndrome fibroblasts to mitomycin C.

Lymphocytes and fibroblasts from people with Bloom syndrome, an autosomal recessive disorder associated with a predisposition to a wide variety of cancers, are known to be hypersensitive to ethylating agents as measured by sister chromatid exchange induction. Recently, hypersensitivity to cell killing by mitomycin C has also been reported in Bloom syndrome fibroblasts from three donors. We report here results which confirm the hypersensitivity of Bloom syndrome fibroblasts as measured by cell killing but show that they have a normal sensitivity to mitomycin C as measured by sister chromatid exchange induction. These results are discussed in terms of their relevance to the diversity of response of Bloom syndrome cells to mutagens, and the nature of the primary defect in Bloom syndrome.

Bloom Syndrome↗
PubMed1985

Mitomycin C (MCC) in advanced soft tissue sarcoma: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

Mitomycin C at a dose of 12 mg/m2 i.v. q 3 weeks was administered to 34 patients with measurable progressive advanced soft tissue sarcomas. No objective response was observed although in one of the 12 patients with overall stabilisation of disease a partial response was reported in lung lesions. The side-effects observed in this group of patients were generally mild. On the basis of this result the application of mitomycin C in this disease cannot be recommended.

Adult↗