THE EFFECT OF ARSENICALS ON ALKALOID PRODUCTION BY CELL-SUSPENSION CULTURES OF CATHARANTHUS-ROSEUS

The effect of arsenic compounds on indole alkaloid production by cell suspension cultures of Catharanthus roseus was investigated. The analysis of indole alkaloids was achieved by using thermospray liquid chromatography-mass spectrometry (LC MS) which facilitated the rapid screening of alkaloid composition in cultures treated with different arsenicals at different times in their growth cycle. Treatment with dimethylarsinate (DMA), a non-selective herbicide, has a drastic inhibitory effect on alkaloid production although it is the least toxic arsenical to growth. Tryptamine, an early precursor in the biosynthesis of indole alkaloids, accumulates in cells treated with DMA, indicating that the initial step of condensation of tryptamine with secologanin is inhibited. Treatment with DMA during the early stationary phase of culture growth enhances the accumulation of some alkaloids, although some, such as catharanthine, are suppressed. The arsenicals arsenate and methylarsonate (MMA) have an inhibitory effect on alkaloid production when applied during the early growth stages. In contrast to MMA and DMA, arsenate has a stimulatory effect on catharanthine production when introduced to the culture during its early stationary phase. Thus the changes in the pattern of alkaloid accumulation on addition of arsenicals are dependent on the arsenic species and its concentration, as well as the time of application. This variable response indicates that each arsenical has a distinct mode of action on the secondary metabolic pathways of C. roseus.