Fig. 1 Comparison of chemical structures. I report here on the antiviral and antitumour activity of hydroxyguanidine (Fig. 1). Hydroxyguanidine combines the imino-group of guanidine, an antiviral agent89, with the hydroxyamino group of hydroxyurea, a drug which has experimental and clinical antitumour activity10"12. Hydroxyguanidine sulphate ((NH2C : NHNHOH)2 H2SO4-H2O, MW 266.24) was used in these experiments and was dissolved in water shortly before use. Hydroxyguanidine was examined for in vitro activity against the Moloney sarcoma virus-Rauscher pseudotype M-MSV (RLV) by assaying for its effect on focus forming units and for in vitro cytotoxic effects (inhibition of cell growth) in four tumour lines: leukaemias L1210 and L5178Y, Novikoff hepatoma and Walker 256 carcinosarcoma13. In addition, it was examined for activity in vivo against four experimental tumours; mast cell P815, leukaemia P388, leukaemia LI210 and carcinosarcoma Walker 256. All tumours were inoculated intraperitoneally and treatment with hydroxyguanidine began 24 h after inoculation and continued until death or for 30 days. The animals were treated with intraperitoneal injections of hydroxyguanidine once a day and at least four dose levels of hydroxyguanidine were used in each experiment. Results are reported as percentage increase in median survival time over that of untreated controls.Table 1 Activity of Hydroxyguanidine Sulphate against Various Experimental Tumours Range of Optimal % Increase indoses daily median survival Tumour tested dose time over that(mg/kg) (mg/kg) of controls Mast cell P815 300-600 500 116Leukaemia P388 300-600 500 145 ~ Leukaemia LI 210 200-800 600 90Carcinosarcoma W-256 200-500 200 > 1,000All rats at this dose level are alive and tumour free more than 5 months after inoculation. The dose of hydroxyguanidine necessary for 50% inhibition (ID50) of Moloney sarcoma virus as assayed by reduction in focus forming units as compared with controls was 2 ug/ml. Hydroxyguanidine also had cytotoxic effects against four tumour lines in vitro. The ID50 as assayed by reduction in cell growth at 24 h was 100 ug/ml. for leukaemia L1210 and leukaemia L5178Y and 25 ug/ml. for Novikoff hepatoma cells. The dose necessary for 50% inhibition of growth of Walker 256 carcinosarcoma cells in vitro at 48 h was also 25 ug/ml.In addition to its antiviral and cytotoxic effects in vitro, hydroxyguanidine also has antitumour activity in vivo against various experimental tumours (Table 1). Hydroxyguanidine produced increases in survival time of 90% and 145% in mice bearing leukaemia L1210 and leukaemia P388 respectively. It was also active in mice bearing the mast cell tumour P815 and rats bearing Walker 256 carcinosarcoma. The effect of hydroxyguanidine against other oncogenic viruses and other tumours both in vitro and in vivo is under investigation. However, it seems likely that moieties of other antiviral agents combined with moieties of antitumour drugs may well yield other compounds with potent dual chemotherapeutic activity.