Tumor promoter-like activity of the molluscicidal latex of 'Crown-of-Thorns' (Euphorbia milii var. hislopii) in the V79 metabolic cooperation assay

The latex of 'Crown-of-Thoms'(Euphorbia miliivar. hislopii, syn. E. splendens) has been shown to be a potent plant molluscicide that could be used against the snails which are intermediate hosts of Schistosoma trematodes. However, a comprehensive toxicological evaluation of the latex is necessary before its large-scale use in schistosomiasis control becomes possible. In fact, one cause for concern is the presence of tumor-promoting phorbol esters in several plants of the Euphorbiaceae family. Phorbol esters as well as a number of other known tumor promoters share the common property of inhibiting metabolic cooperation (i.e., exchange of low molecular weight molecules via gap junctions) between Chinese hamster V79 cells in monolayer cultures. The present study was undertaken to determine if latex of E. milii presents tumor promoter-like activity in this shortterm in vitro assay. Samples of lyophilized E. milii latex were tested at a noncytotoxic concentration range (1, 10, 50 and 100 mug/ml) in three independent experiments. 12-0-Tetradecanoylphorbol-13-acetate (10 ng/ml) was used as positive control. In all three assays, E. milii latex consistently inhibited metabolic cooperation between V79 cells at concentrations (10 mug/ml. These results indicate that E. milii latex contains tumor-promoting substances. These findings suggest that the use of crude latex as a molluscicide may pose a carcinogenic hazard to people who are continuously exposed to the product.

Absence of genotoxic activity of beta-myrcene in the in vivo cytogenetic bone marrow assay

beta-Myrcene (MYR, 7-methyl-3-methylene-1,6 octadiene) is a peripheral analgesic substance and one of the major constituents of lemongrass oil (Cymbopogon citratus, Stapf), a plant widely used in Brazilian folk medicine. In the present study the genotoxicity of MYR was evaluated in vivo using the rat bone marrow cytogenetic assay. Male and female Wistar rats weighing 250 g (223 to 286 g) and 178 g (168 to 186 g), respectively, were used. Two or four rats of either sex were treated orally with MYR (0.1, 0.5 and 1.0 g/kg po), corn oil (negative control) and cyclophosphamide 30 mg/kg ip (positive control). Animals were sacrificed and bone marrow cells were harvested 24 and 48 h after MYR administration. The mitotic index and the frequency of chromosome aberrations were evaluated. Fifty metaphase cells were examined per animal. A dose related increase in mitotic index was observed 24-h after MYR administration. No evidence of MYR-induced clastogenicity was observed under the experimental conditions of this in vivo assay. The present results and previous negative findings of in vitro mutagenicity tests strongly indicate that MYR is not a genotoxic substance