Catharanthus roseus plantlets were inoculated with differentAgrobacterium rhizogenes strains. This plant species is known to produce secondary metabolites and axenic hairy-root cultures are an alternative to extraction of plant tissue for the compounds which are synthesized in roots. Hairy root lines were established from inoculations with the agropine strain 15834 and transformed plants were obtained after spontaneous regeneration. Phenotypic alterations of both the root system and the aerial parts were observed in transformed plants. All the tissues analyzed contained agropine and mannopine. T-DNA analysis confirmed the presence of TL- and TR-DNAs either as distinct inserts, or as a single and continuous insert including the region between TL and TR on pRi 15834.

S 16020, a new 9-OH olivacine derivative, is a novel topoisomerase II inhibitor with activity in cell lines presenting the classical multidrug resistance phenotype. This report summarizes, in addition to pharmacokinetic data, the whole phase I clinical experience of S 16020 using three different infusion schedules. Asthenia and skin toxicity were the main side effects. In an attempt to understand the skin toxicity mechanism, experiments in animals were performed, the results of which are reported. S 16020 showed rapid tumor necrotizing activity in some patients, with soft tissue metastases of epidermoïd tumors and pain at the tumor site. To document the side effects of S 16020 and tumor site reactions (pain, edema, inflammatory signs), inflammatory parameters and some cytokines were measured. In our patients there was no hemolysis and no detection of anti-S 16020 antibodies, confirming the absence of immunogenicity of the compound. Based on the overall data of the three infusion schedules of S 16020, the dose of 100 mg/m(2) over 3 h every 3 weeks was selected for phase II studies.

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