Studies on the mechanism of action of 5-aziridinyl-2,4-dinitrobenzamide (CB 1954), a selective inhibitor of the Walker tumour

CB 1954, a monofunctional alkylating agent, has exceptional activity against the Walker carcinoma yet is inactive against a large number of other animal tumours. A line of the Walker tumour with acquired resistance to CB 1954 was cross-resistant to Melphalan, implying a common mechanism of action, although other tumours highly sensitive to Melphalan were not affected by CB 1954. CB 1954 was also similar to Melphalan in its effects on DNA and RNA synthesis. No correlation was observed between binding of CB 1954 to the DNA of tumour cells and their sensitivity to it. Differences in response of the Walker tumour when incubated with Melphalan and CB 1954 suggest that the latter agent may have some features of an anti-metabolite. In preliminary experiments, its selective anti-tumour effect against the Walker carcinoma has been completely reversed by an intermediate in purine biosynthesis.