Mitomycin A

Mitomycin A is a bacterial metabolite originally isolated from S. caespitosus.¹ It reduces migration inhibition factor (MIF) production by isolated human lymphocytes when used at a concentration of 0.25 µg/ml and decreases spontaneous migration of WEHI-3 murine monocytes when used at concentrations of 0.5 and 5 µg/ml.² Mitomycin A forms intra- and interstrand adducts with DNA in the presence of thiols, such as dithiothreitol (DTT).³ It reduces tumor growth in P388 leukemia and B16 melanoma mouse models with a minimum effective dose (MED) of 0.05 mg/kg for both but is toxic to mice with an LD₅₀ value of 2 mg/kg.^4,1

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1. Hata, T., Sano, Y., Sugawara, R., et al. Mitomycin, a new antibiotic from Streptomyces. I. J. Antibiot. (Tokyo) 9(4), 141-146 (1956).

2. van der Nat, J.M., Beijnen, J.H., van Dijk, H., et al. Suppression of migration inhibition factor (MIF) production by mitomycins in vitro. Immunobiology 172(1-2), 120-127 (1986).

3. Paz, M.M., Das, A., Palom, Y., et al. Selective activation of mitomycin A by thiols to form DNA cross-links and monoadducts: Biochemical basis for the modulation of mitomycin cytotoxicity by the quinone redox potential. J. Med. Chem. 44(17), 2834-2842 (2001).

4. Sami, S.M., Iyengar, B.S., Remers, W.A., et al. Preparation and antitumor activity of new mitomycin A analogues. J. Med. Chem. 30(1), 168-173 (1987).