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PubMed2001

Creating a stable tympanic membrane perforation using mitomycin C.

OBJECTIVE: To determine the ability of topically applied mitomycin C to create a stable tympanic membrane perforation. STUDY DESIGN AND SETTING: Twenty-four rats underwent subtotal removal of the tympanic membranes bilaterally. Forty ears received 0.2 mg/ml of mitomycin C. The remaining 8 received phosphate-buffered saline solution (control). Photographs taken every 3 to 5 days for 44 days were digitally scanned and computer analyzed to calculate the percentage of residual perforation. Application of solutions, photography, and data analysis were performed in a blinded fashion. RESULTS: The mitomycin C treated ears had delayed closure time and healing rate (from day 0 to 25) compared to the control group. All controls healed by day 14. By day 44, 92.5% of the mitomycin C treated ears healed. CONCLUSION: Mitomycin C prolongs the closure and healing rate of myringotomies in rat tympanic membranes. SIGNIFICANCE: Myringotomy with concurrent mitomycin C application may be useful for creating an animal model for chronic tympanic membrane perforation and should be tested in human beings as a method to maintain myringotomy patency for long-term ventilation.

Alkylating Agents↗
PubMed1995

Preoperative mitomycin-C subconjunctival injection and glaucoma filtering surgery.

Intraoperative mitomycin-C application has been well accepted recently as a useful adjunctive procedure to enhance the filtering effect in glaucoma surgery. However, the exact dose of mitomycin-C left after such a procedure in the ocular tissue is variable and unclear. It is important to determine such residual because of potential long-term toxicity of mitomycin-C to the eye. Based on previous successful experience using preoperative mitomycin-C subconjunctival injection in the THC-YAG laser sclerostomy on rabbits, the effect of intraocular pressure (IOP) control and its clinical observation was studied in six eyes of six refractory and high risk glaucoma patients by subconjunctival 1.2 micrograms to 3.6 micrograms mitomycin-C injection 24 to 72 hours prior to classic, routine, limbal-based trabeculectomy surgery. After 18 months of satisfactory clinical observation of the first eye for IOP, functioning bleb appearance and smooth clinical course, the same procedure was used on an additional five eyes, with a follow-up period of more than five months. Average IOP was reduced from 27.8 mm Hg (range 24 to 34 mm Hg) preoperatively to 9.5 mm Hg (range 5 to 14 mm Hg) postoperatively, with a smooth clinical course. The advantages of such preoperative subconjunctival mitomycin-C injection are emphasized here.

Adolescent↗
PubMed1994

Genetic analysis of mitomycin C-hypersensitive Chinese hamster cell mutants.

The genetic diversity of Chinese hamster cell mutants exhibiting hypersensitivity to the bifunctional alkylating agent mitomycin C has been examined. The eight mutants irs3, VH4, UV1, MC5, MMC1, MMC3, MMC4 and MMS2, are between 4- and 30-fold more sensitive to mitomycin C than their respective wildtype parental lines. A number of the mutants show phenotypic similarities to cultured cells from the human cancer-prone syndrome Fanconi's anaemia. Hybrids were formed between pairs of mutants using the thioguanine/ouabain resistant (TOR) hybridization and hypoxanthine/aminopterin/thymidine (HAT)/ouabain selection system and the mitomycin C response of pooled populations of hybrids assessed by constructing survival curves. In every case, hybrids formed between pairs of mutants exhibited a mitomycin C response indistinguishable from that of wildtype cells, indicating complementation. Therefore, the eight mutant lines examined represent eight distinct complementation groups for mitomycin C-hypersensitivity. The results are in contrast to the complementation analysis of UV-sensitive Chinese hamster cell mutants and indicate that the response of mammalian cells to mitomycin C-induced DNA damage is complex and involves a large number of genes.

Animals↗
PubMed1999

Mitomycin C continuous infusion as salvage chemotherapy in pretreated patients with advanced gastric cancer.

UNLABELLED: Our purpose was to evaluate the safety and therapeutic activity of continuously infused mitomycin C in patients with recurring or progressive metastatic gastric cancer following first-line chemotherapy. Patients were treated with mitomycin C 20 mg/m2 i.v. over a time period of 120 h followed by a 3-week rest period. All patients received prednisone 50 mg p.o. prophylactically for 5 days to prevent hemolytic uremic syndrome and pulmonary side effects. Twenty-two consecutively enrolled patients were assessable for toxicity and 20 for response evaluation completing at least one full course of chemotherapy (two patients evaluable but not measurable). PATIENT CHARACTERISTICS: median age: 63 years (39-76); Sex (M/ F): 13/9; median Karnofsky status: 70% (50-100%); resection of primary tumor n = 12 (55%); sites of metastases: liver n = 17 (77%), locally advanced n = 10 (45%), peritoneum n = 13 (59%), lungs n=5 (23%), bone n=3 (14%) and lymph nodes n=14 (64%). Previous chemotherapy regimens: bolus 5-FU/folinic acid n=6 (27%), ELF n=4 (18%), EAP n=3 (14%) and continuous 5-FU/folinic acid/cisplatin/paclitaxel n=9 (41%). In 20 evaluable patients one complete and five partial remissions were observed; overall response rate 30.0% [95% confidence interval (CI): 9.1-50.9%] with a median response duration of 2.1 months (range: 2-6). The median survival was 3.6 months (95% CI: 2.1-6.0) resulting in a 6-month survival rate of 30% since start of mitomycin C. WHO grade III/IV mucositis, diarrhea and fever/infection occurred in 9% of patients each. Cumulative thrombo- and leukocytopenia (WHO grade II/IV) were observed in four and two patients, respectively. Treatment had to be stopped early in two patients. No severe renal dysfunction, pulmonary toxicity or evidence of hemolytic uremic syndrome was observed. Fatigue during the 120 h infusion of mitomycin C was common (11 of 22 patients). We conclude that continuous infusion of mitomycin C is feasible on an outpatient basis, revealing an acceptable toxicity. Mitomycin C demonstrates single-agent activity in pretreated gastric cancer, but has only limited efficacy following cisplatin/paclitaxel-based first-line chemotherapy.

Adult↗
PubMed2000

Intraoperative mitomycin C in the treatment of pterygium.

PURPOSE: To evaluate the effectiveness of intraoperative mitomycin C in preventing the recurrence of primary pterygium. METHODS: In this prospective, randomized study, 38 eyes of 35 patients with primary pterygium were evaluated. In 19 eyes, the "bare sclera technique" combined with intraoperative application of 0.2 mg/mL (0.02%) mitomycin C for five minutes was performed (mitomycin C treated group). The other 19 eyes--taken as control group--underwent surgical excision alone. Statistics were analyzed using the Mann-Whitney U test and the Fischer's exact test. RESULTS: Patients were 20-38 years of age. The mean age was 25.29 +/- 5.08 in the mitomycin C treated group and 25.00 +/- 5.19 in the control group. During the mean follow-up of 17.04 months (range, 12-36 months; SD = 5.89), 4 recurrences (21%) were observed in the mitomycin C treated group and 11 (57.8%) in the control group. The difference between the two groups was significant (p = 0.045). No postoperative complication was encountered in both groups except for recurrences. CONCLUSION: Intraoperative mitomycin C was found to be effective in preventing the recurrence of primary pterygium.

Adult↗
PubMed2002

Mitomycin C therapy for conjunctival-corneal intraepithelial neoplasia.

PURPOSE: To evaluate the efficacy and safety of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). METHODS: One patient with primary CCIN received seven applications for 3 minutes of mitomycin C 0.02%, for 2 weeks, on alternative days. The size of the CCIN before and after the treatment and ophthalmic mitomycin C related complications were evaluated. RESULTS: The lesion started to regress during the second month after the last application of mitomycin C, and by the third month it disappeared completely. The patient remains disease free after 36 months follow up. The complications of mitomycin C included a mild tearing and a slight conjunctival hyperemia that resolved 7 days after the end of the therapy. CONCLUSION: Multiple applications of mitomycin C could be an effective treatment for selected cases of CCIN.

Aged↗
PubMed1999

Preservation of function and histologic appearance in the injured glottis with topical mitomycin-C.

OBJECTIVE: To evaluate the functional and histological effects of a single application of topical mitomycin-C after laser injury in the posterior canine glottis. STUDY DESIGN: A prospective, randomized study of 16 canines. METHODS: A supersaturated (1%) solution of topical mitomycin-C was applied to a unilateral, laser-induced injury near the cricoarytenoid joint in eight dogs. The mitomycin-soaked pledget was placed immediately after induction of the injury and was left in contact with exposed cartilage for 3 minutes. The opposite side was not injured to provide an internal control. In eight additional dogs, the same laser injury was allowed to heal untreated. After 6 weeks, the animals were sacrificed and their larynges harvested. Arytenoid adduction sutures were placed bilaterally, and the force required to bring the vocal folds to midline was measured for each side using tensiometry. Gross and microscopic histological analysis was performed. Statistical analysis was accomplished using a two-tailed Student t test of unpaired samples, and the Wilcoxon Signed Rank Test where appropriate. RESULTS: The mitomycin-C treated larynges demonstrated improved cricoarytenoid joint mobility (P = .007), decreased granulation tissue development (P = .03), and complete prevention of secondary "vocal granuloma" formation (P = .0004) when compared with eight dogs with identical laser injuries allowed to heal untreated. No complications were noted. CONCLUSIONS: This study demonstrates functional preservation and improved histological appearance of the injured glottis after a single treatment with topical mitomycin-C. Potential applications of these findings include prophylactic use of topical mitomycin-C on glottic insults that commonly progress from granulation tissue formation to scarring and decreased vocal fold function.

Administration, Topical↗
PubMed2004

Clinical and histological healing of surgical wounds treated with mitomycin C.

OBJECTIVES/HYPOTHESIS: The proven ability of mitomycin C to inhibit fibroblasts in vitro has stimulated its use in research animals and in humans to control healing. The objective of the study was to follow the healing process of surgical wounds in the dorsum of rats treated topically with mitomycin C. STUDY DESIGN: Prospective experimental study. METHODS: Two distinct surgical wounds were made to the dorsum of 10 adult rats. One of the wounds received topical mitomycin C diluted at 0.5 mg/mL during a 5-minute period, and the other wound was used as a control. The healing process was followed clinically and histologically after the rats were killed at different post-treatment periods. The degree of fibrosis was evaluated histologically by two different pathologists. RESULTS: Surgical wounds treated with mitomycin C presented delayed healing when compared with the untreated wounds, with remission of scabs 7 days after the control wounds. Histological analysis at 1 month after treatment revealed a significant reduction in fibrosis of the wounds treated with mitomycin C when compared with the untreated wounds. After the third month the degree of fibrosis was comparable in both wounds. CONCLUSION: Topical mitomycin C delays the healing of surgical wounds in rats up to the fourth week following treatment, but the degree of fibrosis is comparable in both treated and untreated wounds after 12 weeks. In otolaryngology this characteristic of the drug may be useful in the treatment of external ear canal stenosis, choanal atresias, nasal cicatricial stenosis, laryngeal stenosis, and keloids.

Administration, Topical↗
PubMed2004

Mitomycin does not prevent laryngotracheal repeat stenosis after endoscopic dilation surgery: an animal study.

OBJECTIVES/HYPOTHESIS: Conflicting data exist in the literature regarding the role of mitomycin in the prevention and treatment of laryngotracheal stenosis. The purpose of the study was to assess the value of mitomycin in preventing repeat stenosis after endoscopic dilation surgery of well-established stenoses. STUDY DESIGN: Prospective controlled animal study. METHODS: Laryngotracheal stenosis was induced in 16 dogs. After a period of 3 months the dogs underwent endoscopic dilation and were randomly divided into two groups. The control group received immediate topical application of normal saline. Dogs in the mitomycin group received immediate topical application of 0.5 mg mitomycin. The animals were then observed for 3 more months before euthanasia. The laryngeal lumens were measured endoscopically at baseline, before dilation, and before euthanasia. A comparison was made between the two study groups by means of the Wilcoxon rank-sum test for change in the percentage of stenosis attained by the endoscopic dilation. RESULTS: Nine dogs were included in the control group, and seven in the mitomycin group. Group comparison for initial occlusion before endoscopic dilation using Wilcoxon rank-sum test showed no difference between the two groups (z = 0.16 [P =.87]). Three months after endoscopic dilation, no difference was observed between the two groups regarding the change in the percentage of occlusion (z = -0.21 [P =.83]). CONCLUSION: Mitomycin exerts a benefit equal to that of normal saline when applied to a well-established laryngotracheal stenosis in dogs and does not prevent repeat stenosis after endoscopic dilation surgery.

Alkylating Agents↗
PubMed2005

Comparison of amniotic membrane graft alone or combined with intraoperative mitomycin C to prevent recurrence after excision of recurrent pterygia.

PURPOSE: Without effective adjunctive therapy, the recurrence rate after excision of recurrent pterygia is high. In an effort to determine a way to better reduce the recurrence of pterygia, we compared the efficacy and safety of amniotic membrane graft (AMG) alone and AMG combined with intraoperative mitomycin C after excision of recurrent pterygia. METHODS: Patients with recurrent pterygia were randomly assigned to receive excision of pterygia followed by AMG alone or AMG combined with intraoperative 0.025% mitomycin C for 3 minutes (AMG-mitomycin C). Patients who could be followed up for more than 12 months were entered for data analysis. Conjunctival (potential) and corneal (true) recurrence of pterygia and other complications were recorded. RESULTS: The group receiving AMG alone was made up of 48 eyes in 48 patients, and the group receiving AMG-mitomycin C consisted of 47 eyes in 46 patients. No significant difference was found in age distribution, sex distribution, or duration of follow-up between the 2 groups. Regarding the recurrence rates of each group, 6 conjunctival (12.5%) and 6 corneal (12.5%) recurrences developed in the AMG group, and 4 conjunctival (8.5%) and 6 corneal (12.8%) recurrences developed in the AMG-mitomycin C group. No significant difference was found in the conjunctival and corneal recurrence rate between the 2 groups (P=0.623 and 0.966, respectively; log rank test), and no major complications developed in either group. CONCLUSIONS: AMG alone can be considered an effective alternative adjunctive treatment of recurrent pterygia. The addition of intraoperative mitomycin C did not further reduce the recurrence rate.

Adult↗
PubMed2006

Topical application of mitomycin C to the middle ear is ototoxic in the gerbil.

HYPOTHESIS: Mitomycin C is ototoxic when applied topically to the structures of the middle ear. BACKGROUND: Mitomycin C is a topically applied medication widely used in a variety of surgical procedures to prevent excessive scar tissue formation. Its safety for use during otologic procedures has not been fully evaluated. METHODS: A laboratory study was undertaken using the Mongolian gerbil as an animal model. Both acute and chronic effects on cochlear function of mitomycin C were assessed with measurements of compound action potential (CAP) thresholds of the auditory nerve, CAP input/output functions, distortion product otoacoustic emissions, and endocochlear potentials. Morphologic changes were assessed with light microscopy using hematoxylin-eosin staining as well as transmission electron microscopy. RESULTS: Five-minute applications of mitomycin C (0.5 mg/ml) to the entire surface of the middle ear adversely affected CAP thresholds, input/output functions, distortion product otoacoustic emissions, and the endocochlear potential. Ninety-minute exposures of mitomycin C solely to the round window produced similar changes. Histologic evaluation of animals 1 week after treatment showed damage to cochlear hair cells, the stria vascularis, and spiral ganglion neurons when compared with controls. CONCLUSION: Mitomycin C can produce substantial sensorineural hearing loss when applied topically to the gerbil middle ear for even brief periods. Consequently, its safety for topical use in the human middle ear is highly questionable.

Action Potentials↗
PubMed1996

Long term results of intraoperative mitomycin C in the treatment of recurrent pterygium.

AIM: The study was designed to evaluate the long term results of intraoperative mitomycin C in patients with one recurrence of pterygium. METHODS: In 45 white patients with one recurrence of pterygium the 'bare sclera technique' was performed and a sterile sponge soaked in a 0.2 mg/ml (0.02%) mitomycin C solution was placed intraoperatively on the sclera for 3 minutes. The control group underwent surgical excision only. Recurrences were analysed by the chi 2 test and the method of Kaplan-Meier (life table analysis); the difference between survival curves was tested by the log rank test. The chi 2 test with Yates's correction or Fisher's exact test were used to analyse the difference in complications and side effects between the two groups. RESULTS: After a mean postoperative follow up of 34.55 (SD 13.70) months, 6 recurrences (12.5%) were observed in the mitomycin C treated patients and 16 (35.6%) in the control patients (p = 0.027). The 24 and 48 month life table success rates were 89% and 83% in the mitomycin C treated group and 66% and 63% in the control group, respectively (p = 0.022). No severe side effects appeared during follow up. Superficial punctate keratitis appeared in the early postoperative period in only seven mitomycin C treated eyes (15.5%) (p = 0.018). CONCLUSION: This study confirms the efficacy of intraoperative mitomycin C in improving the success rate after recurrent pterygium surgical excision.

Adult↗
PubMed2000

Comparative study of intraoperative mitomycin C and beta irradiation in pterygium surgery.

AIMS: To compare the rate of recurrence and complication after surgery for primary pterygium performed by one surgeon using either intraoperative mitomycin C or beta irradiation. METHODS: A retrospective study was performed of 164 eyes in 164 patients who had undergone primary pterygium surgery. After the pterygium was excised, the bare sclera was covered by sliding adjacent superior conjunctiva. 103 eyes received intraoperative mitomycin C (0.04%, 150 seconds) and 61 eyes beta irradiation (total dose 21.6 Gy). The mean follow up period was 20.2 (SD 17.9) months (range 1-66 months). Recurrence was defined as the postoperative regrowth of fibrovascular tissue crossing the corneoscleral limbus. RESULTS: The recurrence rate after mitomycin C and beta irradiation was 8.74% and 23.0% of eyes, respectively, after mean follow up of 17.9 and 31.2 months, respectively. The Kaplan-Meier survival analysis revealed a significantly better outcome for those who had intraoperative mitomycin C (Mantel-Cox log rank analysis, p=0.031). The mean interval to recurrence was not significantly different between the two groups. During the follow up, none of the patients showed side effects or reactions related to mitomycin C or beta irradiation. CONCLUSIONS: The intraoperative administration of 0.04% mitomycin C is more effective than beta irradiation as an adjunctive treatment for pterygium surgery in the patient population examined in this study.

Adult↗
PubMed2002

Preoperative topical and intraoperative local mitomycin C adjuvant therapy in the management of ocular surface neoplasias.

AIMS: To demonstrate the efficacy of mitomycin C as adjuvant therapy preoperatively and intraoperatively in the management of recurrent or diffuse ocular surface neoplasias. METHODS: The case notes of 11 patients receiving mitomycin C adjuvant therapy as 0.04% eye drops four times a day in two weekly courses preoperatively and/or a single intraoperative application of 0.4 mg/ml of mitomycin C were reviewed. The histopathology included conjunctival primary acquired melanosis, conjunctival melanomas, sebaceous cell carcinomas with conjunctival intraepithelial spread, and conjunctival intraepithelial squamous neoplasias. Seven patients had additional limited local excision of the residual tumour mass and one had cryotherapy. RESULTS: All cases showed a favourable response to mitomycin C adjuvant therapy with regression in size or retardation of a rapid growth pattern and no serious sequelae. Postoperative follow up of 6-36 months following excision of the lesion with or without intraoperative mitomycin C showed no clinical recurrence in any of the cases. CONCLUSION: In this series, mitomycin C adjuvant therapy of recurrent or diffuse ocular surface neoplasias was well tolerated and showed favourable clinical results.

Administration, Topical↗
PubMed1992

Mitomycin-induced pulmonary toxicity: case report and review of the literature.

OBJECTIVE: This report describes a case of mitomycin-induced pulmonary toxicity and reviews the incidence of this adverse effect, reported patterns of toxicity and associated dosages of the drug, and the use of corticosteroids in the management of pulmonary toxicity. DATA SOURCES: Information about our patient was obtained in part from the medical chart; we had also treated him personally in the past. We conducted a MEDLINE search of the English language literature (restricted to human studies) from 1966 to 1991 and manually searched Index Medicus for current information. STUDY SELECTION: All case reports that described pulmonary toxicity possibly associated with mitomycin were reviewed. DATA EXTRACTION: Studies were evaluated for the dosages of mitomycin given to patients, the nature and onset of symptoms, management course, and corticosteroid use. DATA SYNTHESIS: Our case is similar to others described in the literature. The incidence of mitomycin-induced pulmonary toxicity has been reported to range from 2 to 38 percent. Concurrent vinca alkaloid administration may potentiate the risk of an acute pulmonary insult secondary to mitomycin use. The toxicity is usually of slow onset and the average total dosage of drug implicated is 78 mg. A formal evaluation of corticosteroid treatment has not been performed, but various authors have reported success with different regimens. CONCLUSIONS: The incidence of pulmonary toxicity associated with mitomycin is unpredictable, but more likely to occur at higher dosages. Treatment with corticosteroids is encouraged to improve pulmonary response.

Adrenal Cortex Hormones↗
PubMedDate not supplied

A comparative clinical trial of mitomycin C and cyclosporin A in trabeculectomy.

This prospective, randomized clinical trial assessed the effects of mitomycin C and cyclosporin A used as antimetabolites in trabeculectomy on the post-operative IOP and success rate. Eighty-six consecutive patients were randomly allocated to three treatment groups. There were 30 patients in the mitomycin C group, 28 in the cyclosporin A group and 28 in the control group. The follow-up periods were different for the three groups and ranged from 6 to 30 months. The treatment groups consisted of primary open-angle glaucoma, closed-angle glaucoma, various secondary glaucomas and prior failed trabeculectomy. There were no significant differences pre-operatively with respect to IOP and number of medications used (p > 0.05). Postoperative IOP was considered to be successfully reduced when it was reduced by more than 25% from baseline or when it was lower than 20 mmHg. According to these criteria, IOP was under control in 90% of the mitomycin C treated eyes, 85.7% of cyclosporin A treated eyes and 71.4% of the control eyes. Postoperatively there was a significant decrease in IOP (p < 0.01) and in the number of medications need to control IOP (p < 0.01) in the mitomycin C and cyclosporin A groups. Post-operative IOP and number of medications in the mitomycin C and cyclosporin A group were similar. Complications encountered in the three groups were similar. There were no serious complications like hypotonus maculopathy. Our study highlights the utility of mitomycin C as an adjunct in glaucoma filtering surgery and indicated that cyclosporin A may also be used as an antimetabolite.

Adolescent↗
PubMed1992

Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.

PURPOSE: Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS: Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS: Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS: The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Mitomycin C-induced apoptosis in cultured human Tenon's capsule fibroblasts.

To investigate the mitomycin C-induced apoptotic cell death of fibroblasts, the primarily cultured human Tenon's capsule fibroblasts were exposed to a clinically used dosage of 0.4 mg/ml of mitomycin C for 5 minutes. TUNEL (TdT-mediated dUTP-biotin nick end labeling) assay and electron microscopic studies were performed to determine the extent of mitomycin C-induced apoptosis. A flow cytometric study was performed to quantify the apoptotic cell population over time. The TUNEL stains were positive and electron microscopy showed features of apoptotic cell death in some fibroblasts 3 and 5 days after treatment. Flow cytometric analysis using Annexin V-propidium iodide double staining detected apoptotic cells 3 days after treatment. These apoptotic cell populations increased at 4 days and were sustained for one week. This study revealed that the clinical effects of mitomycin C on fibroblasts may be mediated not only by antiproliferative but also apoptotic cell death to some degree. Therefore, the apoptotic cell death of fibroblasts induced by mitomycin C should be considered to properly understand the mechanism of wound healing after trabeculectomy with adjunctive mitomycin C.

Antibiotics, Antineoplastic↗