formazans and Body-Weight

A paucity of data exists to corroborate the few studies that report immune suppression after exposure to perfluorooctanesulfonate (PFOS). In this study, adult male C57BL/6 mice were exposed to PFOS daily via gavage for 60 days [0, 0.5, 5, 25, 50, or 125 mg/kg total administered dose (TAD)]. The results showed that liver mass was significantly increased at > or =5 mg PFOS/kg TAD and in a dose-dependent manner. Lymphocyte proliferation and natural killer cell activity were altered in male mice. Plaque forming cell (PFC) response was suppressed beginning at 5 mg/kg TAD. Based on the liver mass and PFC response, the no observed adverse effect level and lowest observed adverse effect level for male mice exposed PFOS for 60 days was 0.5 and 5 mg/kg TAD, respectively. Measured PFOS serum concentrations at these dose levels were 0.674 +/- 0.166 and 7.132 +/- 1.039 mg/l, respectively. These results indicate that PFOS exposure can affect the immunity function in mice at levels approximately 50-fold for highly exposed human populations.

Topics: Administration, Oral; Alkanesulfonic Acids; Animals; Body Weight; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorocarbons; Formazans; Hemolytic Plaque Technique; Immune System; Kidney; Killer Cells, Natural; Liver; Lymphocyte Subsets; Lymphocytes; Male; Mice; Mice, Inbred C57BL; No-Observed-Adverse-Effect Level; Organ Size; Random Allocation; Spleen; Tetrazolium Salts; Thymus Gland; Time Factors

Among the Cyanoprokaryota (blue-green algae), the genus Phormidium has thus far rarely been studied with respect to toxin production and potentially resulting human and environmental health effects. We here show that five previously unexplored freshwater species of this genus (Ph. bijugatum, Ph. molle, Ph. papyraceum, Ph. uncinatum, Ph. autumnale) are indeed capable of producing bioactive compounds. Phormidium extracts caused weight loss as well as neuro/hepatotoxic symptoms in mice, and in the case of Ph. bijugatum even death. Very low levels of saxitoxins and microcystins, as confirmed by ELISA, were insufficient to explain this toxicity and the differing toxic potencies of the Phormidium species. Qualitative HPLC analyses confirmed different substance patterns and in the future could aid in the separation of fractions for more detailed substance characterisation. The results in vivo were confirmed in vitro using cells of human, mouse and fish. The fish cells responded least sensitive but proved useful in studying the temperature dependence of the toxicity by the Phormidium samples. Further, the human cells were more sensitive than the mouse cells thus suggesting that the former may be a more appropriate choice for studying the impact of Phormidium to man. Among the human cells, two cancer cell lines were more responsive to one of the samples than a normal cell line, thereby indicating a potential anti-tumour activity. Thus, the five freshwater Phormidium species should be considered in environmental risk assessment but as well, as a source of therapeutic agents.

Topics: Animals; Bacterial Toxins; Body Weight; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Cyanobacteria; Enzyme-Linked Immunosorbent Assay; Fishes; Fluorescent Dyes; Formazans; Humans; Liver; Male; Mice; Microcystins; Peptides, Cyclic; Saxitoxin; Species Specificity; Statistics, Nonparametric; Tetrazolium Salts