5-Hydroxymethyl-2′-deoxyuridine, a normal DNA constituent in certain Bacillus subtilis phages is cytostatic for mammalian cells

Abstract

WE have described¹ the discovery of cytostatic action on cultured Ehrlich ascites carcinoma cells of a series of deoxyuridines substituted in the carbon-5-position (for example, 5-hydroxymethyl-, 5-mercaptomethyl-, 5-cyano-, 5-thiocyanato- and 5-vinyl-2′-deoxyuridine), the strongest effect being shown by 5-hydroxymethyl-2′-deoxyuridine (HMUdR). Although Green et al. reported² that the compound inhibits growth and cell division of Escherichia coli ${\text{15}}_{{\text{T}}^{–}}$, no reports of any inhibitory properties have to our knowledge appeared since 1957. It was found, however, that HMUdR is a normal constituent of the DNA of certain Bacillus subtilis phages^3–5, in which it replaces all the thymidine, and a number of reports have described its chemical synthesis^6–11. We indicate here, however, that the strong effect of the compound on Ehrlich ascites carcinoma cells is not the result of an anomalously high sensitivity of these cells in the culture conditions used, but is a more general phenomenon also found with other cell lines and in vivo.