CHANGES IN PLASMA 5-S-CYSTEINYLDOPA CONCENTRATION IN B16 MELANOMA-BEARING MICE TREATED WITH INTERFERON-BETA OR DACARBAZINE

We have previously shown that the urinary excretion of 5-S-cysteinyido pa (5-S-CD) reflects well the progression of B16 mouse melanoma. We ex amined the usefulness of plasma concentration of 5-S-CD in following t he progression of melanoma and evaluating the efficacy of immuno- and chemotherapeutic agents in the B16 mouse model. Murine interferon-beta (MuINF-beta; 3 x 10(5) U) or dacarbazine (DTIC; 50 mg/kg) was adminis tered once a day for 10 or 5 consecutive days starting 8 days after su bcuteneous inoculation of B16 melanoma cells in C57BL/6 mice. Blood sa mples were collected from the tall vein and tumour volumes were measur ed every other day until day 24. Levels of 5-S-CD in plasma were deter mined by high-performance liquid chromatography. Tumours became palpab le on day 6-8 and grew exponentially thereafter in the control mice. T umours in INF-beta-treated mice also grow exponentially, although at a reduced rate. However, the growth of tumours in the DTIC-treated mice was almost suppressed between days 12 and 18. Mean values of tumour v olume on day 16 were 1.45, 1.05, and 0.83 cm3 in the control, INF-beta -treated, and DTIC-treated groups, respectively. The plasma concentrat ion of 5-S-CD began to increase on day 8, at much slower rates in the experimental groups than those in the control group. Mean values of pl asma 5-S-CD on day 16 were 14.3, 5.9, and 5.6 nmol/l in the control, I NF-beta-treated, and DTIC-treated groups; 5-S-CD level on day -2 was 1 .8 nmol/l. The ratios between plasma 5-S-CD and tumour volume were fou nd to be significantly lower in the INF-beta-treated mice than in the control mice. These results indicate that plasma 5-S-CD is useful in e valuating the efficacy of immuno- and chemotherapeutic agents in exper imental melanomas.