Isohydroxyurea causes a rapid devitalization of E. coli C600. The effect of this agent on bacterial metabolism is manifested mainly in an inhibition in the synthesis of RNA. This is in marked contrast to the biologic action of the isomeric compound, hydroxyurea, which is primarily bacteriostatic in nature and which involves a specific block in DNA production.

The lethal action of isohydroxyurea is accompanied by degradation of cellular DNA. A bacterial strain resistant to the devitalizing action of the drug did not exhibit this degradation. This strain was still, however, blocked in its ability to synthesize RNA. Using bacterial strains resistant to either hydroxyurea or isohydroxyurea, a relationship based on crossresistances was established between the two compounds. A metabolic scheme seeking to relate these and other observations in proposed.

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This is the ninth paper of a series dealing with the effects of hydroxyurea. Paper 8 dealt with the DNA of hydroxyurea-treated bacteria (30). This investigation was aided by USPHS research Grant CA-08374 from the National Cancer Institute. Support was also provided by a contract (Nonr 266 (89) NR 136–574) between the Office of Naval Research, Department of the Navy, and Columbia University.

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©1969 American Association for Cancer Research.
1969
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