Cell Hybridization Study of Resistance to Alkylating Agents

5-Aziridinyl-2,4-Dinitrobenzamide (CB 1954) has been reported to be a highly selective inhibitor of the Walker tumour, with a therapeutic index of 60 (refs. 1 and 2). This compound, however, differs from other tumour inhibitory alkylating agents in that it is monofunctional and fails to inhibit the growth of several animal tumours which respond to difunctional alkylating agents. Compounds closely related in structure to CB 1954 are either much less active or inactive against the Walker tumour³. The structural specificity and biological properties of CB 1954 indicate that its mechanism of action is different from that of the tumour inhibitory difunctional alkylating agents. Whereas the latter are thought to be cytotoxic primarily as a result of their reaction with DNA, CB 1954 may interfere with a specific stage of purine biosynthesis². We have shown by cell hybridization that, unlike resistance to a difunctional alkylating agent, cellular resistance to CB 1954 is lost on fusion with a sensitive cell.