The fate of Lyngbya majuscula toxins in three potential consumers.

Blooms of Lyngbya majuscula have been reported with increasing frequency and severity in the last decade in Moreton Bay, Australia. A number of grazers have been observed feeding upon this toxic cyanobacterium. Differences in sequestration of toxic compounds from L. majuscula were investigated in two anaspideans, Stylocheilus striatus, Bursatella leachii, and the cephalaspidean Diniatys dentifer. Species fed a monospecific diet of L. majuscula had different toxin distribution in their tissues and excretions. A high concentration of lyngbyatoxin-a was observed in the body of S. striatus (3.94 mg/kg(-1)) compared to bodily secretions (ink 0.12 mg/kg(-1); fecal matter 0.56 mg/kg(-1); eggs 0.05 mg/kg(-1)). In contrast, B. leachii secreted greater concentrations of lyngbyatoxin-a (ink 5.41 mg/kg(-1); fecal matter 6.71 mg/kg(-1)) than that stored in the body (2.24 mg/kg(-1)). The major internal repository of lyngbyatoxin-a and debromoaplysiatoxin was the digestive gland for both S. striatus (6.31 +/- 0.31 mg/kg(-1)) and B. leachii (156.39 +/- 46.92 mg/kg(-1)). D. dentifer showed high variability in the distribution of sequestered compounds. Lyngbyatoxin-a was detected in the digestive gland (3.56 +/- 3.56 mg/kg(-1)) but not in the head and foot, while debromoaplysiatoxin was detected in the head and foot (133.73 +/- 129.82 mg/kg(-1)) but not in the digestive gland. The concentrations of sequestered secondary metabolites in these animals did not correspond to the concentrations found in L. majuscula used as food for these experiments, suggesting it may have been from previous dietary exposure. Trophic transfer of debromoaplysiatoxin from L. majuscula into S. striatus is well established; however, a lack of knowledge exists for other grazers. The high levels of secondary metabolites observed in both the anaspidean and the cephalapsidean species suggest that these toxins may bioaccumulate through marine food chains.

Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A).

Lyngbyatoxin A is produced by marine algae, and causes local cutaneous toxicity in swimmers. The purpose of this research was (1) to determine the partition coefficient of lyngbyatoxin A in octanol/water and (2) to use methods in vitro to measure the penetration and distribution of lyngbyatoxin A in guinea pig and human skin. Discs of excised guinea pig and human skin were mounted in diffusion chambers that exposed the epidermal surface to air and bathed the dermis with HEPES-buffered Hanks' balanced salt solution with gentamicin sulphate. The epidermal surfaces were dosed with 26 micrograms lyngbyatoxin A/cm2 dissolved in 13 microliters dimethyl sulphoxide/cm2. The diffusion chambers were incubated at 36 degrees C for varying periods (1.0-24 hr). HPLC was used to quantify lyngbyatoxin A. Skin penetration was calculated by summing the amount of lyngbyatoxin A recovered from the dermis and receptor fluid. The mean partition coefficient for lyngbyatoxin A was 1.53. Penetration of lyngbyatoxin A (expressed as a percentage of dose, n = 3) in guinea pig and human skin was 23 and 6.2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time.

Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin.

To investigate the interaction between tumor promoters and their cellular targets, 6 new fluorescent derivatives of indole alkaloid tumor promoter teleocidin were synthesized from (-)-indolactam V, and examined for induction of Epstein-Barr virus, binding ability to the TPA receptor on mouse skin and activation of protein kinase C. (-)-7-(2-N-Dansylaminoethyl)indolactam V (dansyl-ILV) had strong activities and proved to be a potent tumor promoter in a 2-stage carcinogenesis experiment. (-)-2-Formyl-7-decanoyl-indolactam V (FD-ILV) showed a weak but significant activity. The other 4 derivatives had little activity. Treatment of HeLa cells with dansyl-ILV and FD-ILV resulted in intense fluorescence in the entire cytoplasm and on the nuclear membrane. Inactive or less active derivatives with hydrophobicity similar to that of dansyl-ILV showed significant cytoplasmic fluorescence, and those far less hydrophobic than dansyl-ILV or far more hydrophobic than FD-ILV showed little fluorescence. This suggested that hydrophobicity rather than biological activity determines the cellular uptake of these fluorescent probes.