Studies on the mechanism of action of mitomycin C.
The in vitro formation and properties of the molecular complex between mitomycin C and native DNA were examined by means of various experimental methods; the data obtained indicate that the complex is extremely weak and that the chromophoric moiety of the antibiotic is not involved in its formation. The alkylating activity of mitomycin C was also studied using 3H-mitomycin C; while monofunctional alkylation increases almost in parallel with the concentration of the antibiotic, the difunctional alkylation, causing inter-strand cross-linkages in DNA, rapidly reaches a maximum and then remains constant even when increasing the concentration of the antibiotic and monofunctional alkylation. On the basis of these results, the currently accepted molecular model of the mitomycin--DNA interaction must be revised; a new model of this interaction is presented, which is in better agreement with the properties of mitomycin C and with the latest findings on the subject.
D000478:Alkylation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D003956:Dialysis; D008937:Mitomycins / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D008937:Mitomycins; D004247:DNA