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Cross-resistance studies involving a selected group of anticancer agents, most of which are radiomimetic, and derived mutants of Escherichia coli (strain S) have been undertaken in the hope of providing insight into the mechanism of action of anticancer agents. Despite the complexity of such a task, the data now available indicate that specific patterns of cross-resistance can be induced by these agents. This report will be concerned with cross-resistance relationships between 1-methyl-3-nitro-1nitrosoguanidine-induced resistant mutants of E. coli strain S and 1-chloroethyland 1-chloropropyl-3-nitro-1-nitrosoguanidine, nitrogen mustard, nitromin, azaserine, 6-diazo-5-oxonorleucine, Mitomycin C, penicillin, and ultraviolet light. Following reports will deal with cross-resistance patterns among mutants induced by the other compounds in the above test series. Two assumptions are basic to these studies: the first is that organisms should be cross-resistant to toxic agents similar in chemical composition or mode of action (Szybalski and Bryson, 1952, 1954, 1955; Szybalski, 1953, 1954); and the converse, that cross-resistance between toxic agents indicates a common mechanism of action on the cell. Several of the above compounds were classified as radiomimetic for several reasons. 1-Methyl-3nitro-1-nitrosoguanidine has anticancer activity in mice (Goldin, Venditti, and Kline, 1959; Greene and Greenberg, 1960; Skinner et al., 1960). In bacteria, this compound is mutagenic (Mandell and Greenberg, 1960), it induces filament formation (Kilgore and Greenberg, 1961), and is reversed by sulfhydryl-containing compounds (Greenberg and Morris, 1961). A strain of E. coli selected for resistance to

RESISTANCE AND CROSS-RESISTANCE OF ESCHERICHIA COLI MUTANTS TO ANTICANCER AGENTS. 1-METHYL-3-NITRO-1-NITROSOGUANIDINE