Molecular aspects of microcystin-induced hepatotoxicity and hepatocarcinogenesis.

It is known that microcystin (MC) is a cyanotoxin that is a potent environmental inhibitor of eucariotic protein serine/threonine phosphatase 1 and 2A, both in vitro and in vivo. Consequently, these cyanobacterial toxins (MC-IARC group 2B carcinogen, MC extracts-group 3) are potent tumor promoters and there is an indication that they may also act as tumor initiators. The ability of microcystin-LR (MC-LR) to act as a tumor initiator is based on fact that it can induce DNA damage either by direct interaction with DNA or by indirect mechanisms through formation of reactive oxygen species (ROS). Both acute and chronic exposures, to either low or high doses of MC-LR, can activate apoptotic pathways. Chronic exposure to low concentrations of MC-LR contributes to increased risk for cancer development. Epidemiological studies, in certain areas of China, have suggested that MC is one of the risk factors for the high incidence of primary liver cancer (PLC). Recently, we have reported a correlation between PLC and cyanobacterial "blooms" in reservoirs used as a source for drinking water supply in central Serbia. It appears that the combination of acute and chronic exposures to both high and low doses of MC can lead to PLC initiation and promotion. Based on this, we propose that the requirement for the co-factors such as aflatoxin B1 and other mycotoxins, HBV, HCV, alcohol, etc. is not needed for initiation and promotion of PLC by MC-LR as was suggested earlier. The possible mechanisms of the genotoxicity of MC and its role as a hepatocarcinogen are outlined in this review. Furthermore, we show that the exposure of hepatocytes to MC can lead either to malignant proliferation or apoptosis.

Colonization of wheat (Triticum vulgare L.) by N2 -fixing cyanobacteria: IV. Dark nitrogenase activity and effects of cyanobacteria on natural 15 N abundance in the plants.

Two cyanobacterial soil isolates, Nostoc 2S9B and Anabaena C5, that had previously been shown to form different types of association with the roots of wheat plants grown in liquid culture, were tested for heterotrophic nitrogenase activity and the ability to colonize the roots of plants grown in sand. Nostoc 2S9B showed substantial nitrogenase activity when associated with the roots of plants grown in liquid culture in medium free of combined N, even with the roots maintained and with assays performed in the dark (29 % of the rate shown by root-associated Nostoc 2S9B grown and assayed in the light). When grown heterotrophically in the dark, at the expense of fructose, free-living Nostoc 2S9B showed a similar nitrogenase activity to root-associated Nostoc 2S9B in the dark. In contrast, Anabaena C5 showed no nitrogenase activity in the dark, under these conditions. When three different wheat cultivars were grown in sand that had previously been surface-inoculated with Nostoc 2S9B or with the cultured symbiotic cyanobacterium Nostoc LBG1, isolated from the bryophyte Anthoceros, there was colonization of the plant roots; there was no colonization of roots by Anabaena C5 under these conditions. Some increases in plant biomass and nitrogen content were observed, but these were dependent on the wheat cultivar and cyanobacterial inoculum used. Wheat plants grown in sand that had been pre-inoculated with Nostoc 2S9B, Nostoc LBG1 or Anabaena C5 in medium free of combined N had lower δ15 N values in both roots and shoots than plants grown under identical conditions without a cyanobacterial inoculum. The observed 15 N/14 N fractionation indicates that N2 fixed by the cyanobacteria contributed to the nitrogen economy of the wheat plants, irrespective of whether they were closely associated with the plant roots.