217751a0Nature2175130196802247517520028-0836196810.1038/217751a0ukNatureNatureNATUREnatureNature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public./nature/journal/v217/n5130issueJournal homeArchiveCurrent issueAdvance online publicationPrivacy policySubscribeNature Publishing GroupCurrent issue217751a0Anti-tumour Activity of S-Carbamylcysteine AU - ADAMSON, RICHARD H.Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.L-ASPARAGINASE has been shown to inhibit the growth of various tumours in the mouse, rat and dog and is currently being used in clinical trials1-5. Unlike normal cells, the cells of tumours that respond to this enzyme have a requirement for the nutritionally non-essential amino-acid, L-asparagine.Treatment of tumours with L-asparaginase is tempered, however, by the possibilities of reaction to foreign protein and of endotoxin contamination of the enzyme isolated from E. coli. Several compounds structurally related to L-asparagine were therefore investigated in the hope that these analogues might interfere with the uptake and/or utilization of L-asparagine. S-Carbamyl-L-cysteine (SCO, Fig. 1), structurally related to L-asparagine and L-cysteine, was tested for anti-tumour activity in vitro and in vivo against tumours which were sensitive and non-sensitive to L-asparaginase. SCO has previously shown anti-tumour activity against a transplanted mouse adeiio-carcinoma6. S-Carbamyl-L-cysteine was tested in vitro against L5178Y and L1210 cells in static culture as previously reported7. Cell counts were taken at 24 and 48 h using a Coulter counter. The effects of SCC at various concentrations are reported in Table 1. SCC seemed to be equally cytotoxic against the L5178Y L-asparaginase sensitive and the L1210 non-sensitive cells. Table 1. CYTOTOXIC EFFECT OF S-CARBAMYL-L-CYSTEINE AGAINST CELLS IN TISSUE CULTURE SCC concentration Percentage inhibition of growth of controls Cell line (^g/ml.) at 24 h at 48 h X5178F 50 97 99 25 94 98 10 35 40 5 0 0 [pound]1210 50 68 97 25 61 88 10 26 40 5 0 0 Table 2. ACTIVITY OF S-CARBAMYL-L-CYSTEINE AGAINST VARIOUS TRANSPLANTED TUMOURS Range of Tumour doses used (mg/kg) Optimal dose (mg/kg) Percentage increase in median survival over control Percentage inhibition of average control tumour weight L517SY 50-400 d[ast] 400 eod 30 400eodf Z1210 250-300 d 400 eod 40 . 400 eod P388 300 d 400 eod 37 300-400 eod PI 798 200-300 d 300 dj 70 [ast] d, Daily. eod, Every other day. Five injections (day 1-5), mice killed on day 10 and tumours excised and weighed. S-Carbamyl-L-cysteine was also effective against several tumours in vivo (Table 2). SCC seemed more effective in inhibiting the growth of the P1798, L-asparaginase sensitive lymphosarcoma than in increasing the median survival of mice bearing leukaemias sensitive (L5178Y) or non-sensitive to L-asparaginase. The mechanism of the anti-tumour effect of SCC is unknown, but it, or one of its metabolic products, may interfere with the oxidative energy supply supporting protein synthesis8. The equivalent activity of SCC against L5178Y and L1210 in vitro does not lend support to the hypothesis that SCC is an antimetabolite of L-asparagine. Further studies on the mechanism of action of SCC and studies of the anti-tumour activity of other analogues of L-asparagine are in progress.Kidd, , J. G., J. Exp. Med., 98, 565 (1953).ArticlePubMedISIChemPortBoyse, , E. A., Old, , L. J., and Stockert, , E., Nature, 198, 800 (1963).ArticlePubMedISIChemPortBroome, , J. D., Nature, 191, 1114 (1961).ArticleISIChemPortKwak, , K. S., Jameson, , E., Ryan, , R. M., and Kurtz, , H. M., Cancer Res., 21, 44 (1961).PubMedISIChemPortOld, , L. J., Boyse, , E. A., Campbell, , H. A., Brodey, , R. S., Fidler, , J., and Teller, , J. D., Cancer, 20, 1066 (1967).PubMedISIChemPortSkinner, , C. G., McKenna, , G. F., McCord, , T. J., and Shrive, , W., Texas Rep. Biol. and Med., 16, 493 (1955).Adamson, , R. H., Hart, , L. G., DeVita, , V. T., and Oliverio, , V. T., Cancer Res. (in the press).Rabinovitz, , M., and Fisher, , J. M., J. Nat. Cancer Inst., 28, 1165 (1962).PubMedISIChemPort