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 INTISSUE CULTURE SCCconcentration Percentage inhibition of growth of controls Cell line (^g/ml.) at 24 h at 48 h X5178F 50 97 9925 94 98 10 35 405 0 01210 50 68 97 25 61 8810 26 40 5 0 0Table 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 weightL517SY 50-400 d400 eod 30 400eodfZ1210 250-300 d 400 eod 40 . 400 eodP388 300 d 400 eod 37 300-400 eodPI 798 200-300 d 300 dj 70d, 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.