MITOMYCIN

MITOMYCIN

Brand Names : Mitomycin C; Mitomycine C; NSC-26980;

Mutamycin. Mitocin-C; MMC; Ametycine Mitomycin, m.p. 360°, is an antineoplastic antibiotic produced by the growth of Streptomyces verticillatus or Streptomyces caespitosus. It occurs as a blue-violet crystalline powder. It is soluble in water, acetone, methyl alcohol, butyl acetate, and cyclohexanone. A 0.5% solution in water has a pH of 6 to 8. It is slightly soluble in benzene, carbon tetrachloride, ether; practically insoluble in petroleum ether. It is stored in airtight containers and protected from light.

Unlike most other antibiotics, it is activated in uiuo to a bifunctional or trifunctional alkylating agent. After activation it binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function. Mitomycin C contains three groups that can damage cells; the quinone that can participate infree radical reactions generating superoxides, and aziridinyl and urethane functions that can take part in DNA alkylation. Activation of mitomycin proceeds by means of reduction of the quinone and loss of a methoxy group. This is followed by alkylation of DNA with the formation of interested cross links, resulting in inhibition of DNA synthesis, DNA fragmentation and cell death.

Mitomycin disappears rapidly from the blood after intravenous injection. It is widely distributed and metabolized mainly in the liver. Following normal doses about 10% of a dose is excreted unchanged in the urine; small amounts are also present in bile and faeces.

Uses: Mitomycin is a highly toxic antibiotic with antineoplastic properties. It is used, with other antineoplastic agents, in the palliative treatment of gastric, colon, breast and pancreatic adenocarcinomas as well as certain head, bladder, rectum, lung, cervix and neck tumours and chronic myelogenous leukaemia.

It is also used as a bladder instillation. The short duration of response (1 to 3 months) and the toxicity causing myelosuppression has limited the use of mitomycin as a single agent. It is commonly used with other drugs for the treatment of gastric adenocarcinomas.

Adverse Effect

The main adverse effect of mitomycin is delayed cumulative bone-marrow suppression. Other side-effects include renal damage, pulmonary reactions, gastro-intestinal toxicity, dermatitis, alopecia, fever and malaise.