Biology Reference
In-Depth Information
and Falconer, 1999). This could be due to the tumor-producing activity of MC-LR. On the other hand,
inhibition of cytokinesis at higher concentrations (10 nM) of MC-LR induced apoptosis (Humpage
and Falconer, 1999). Nodularin is reported to activate several proto-oncogenes of the
fos
and
Jun
family that are considered to play a role in tumor promotion (Ohta
et al
., 1994).
vi) Toxicity studies in vitro
:
The viability of mouse B- and T-lymphocytes decreased by 23%
in vitro
treated with MC-LR after 24 h. Apoptotic cell death occurred in B-cells probably through B-cell antigen
receptor and mitochondrial pathway while T-cells were unaffected (Teneva
et al
., 2005a). Isolated rat
hepatocytes treated with MC-LR showed cell shape changes (blebbing) associated with remarkable
reorganization of microfi laments. These changes are specifi c to MC-LR because microfi lament-
modifying drugs like cytochalasin D and phalloidin could not bring out such changes (Eriksson
et al
., 1989). Falconer and Yeung (1992) described cytoskeletal changes in cultured rat hepatocytes
exposed to
Microcystis
toxins. The mechanism of
Microcystis
toxicity is due to cytoskeletal damage
leading to loss of cell morphology, cell adhesion and fi nally cellular necrosis.
Besides hepatocytes, MCs and nodularins can also affect other types of cells. Fladmark
et al
. (1999)
observed apoptosis in human embryo kidney HEK 293 cells, Swiss 3T3 mouse embryo fi broblasts,
breast carcinoma cell line MCF-7 and in rat promyelocytic IPC-81 leukemia cells. Various other cellular
deformities observed were membrane budding, cell shrinkage and organelle redistribution in human
fi broblasts, endothelial cells, epithelial cells, lymphocytes and in rat promyelocytes (McDermott
et
al
., 1998; Mankiewicz
et al
., 2000, 2001). Dose-related increase in chromosomal breakage has been
observed in human lymphocytes (Repavich
et al
., 1990; Premazzi and Volterra, 1993). Treatment of
human and chicken peripheral blood lymphocytes with MC-LR (for 72 h in a proliferation assay)
decreased T-cell proliferation at the highest dose whereas the proliferation of B-lymphocytes was
inhibited at all doses. Apoptotic and necrotic cells increased with dose and time of exposure (Lankoff
et al
., 2004). MC-LR- and MC-RL-containing extracts from bloom material of
M
.
aeruginosa
(growing
in Sulejow Reservoir that serves as a source of drinking water) at acceptable dose of MC (WHO)
caused activation of cytochrome
c
oxidase complex in mitochondria and it is suggested to serve as
an indicator for assessing the toxicity
in vivo
(Majsterek
et al
., 2004). Benthic marine cyanobacterial
species from Portuguese coast (not associated with apparent bloom formation) produced novel toxins
that induced apoptosis in SH-SY5Y-neuroblastoma cells, NRK kidney cells or fi broblasts. Aqueous
extracts of the cyanobacteria inhibited thrombin-induced blood platelet activation, with decreased
P-selection expression, platelet aggregation and shedding of platelet-derived microvesicles. Two of
the cyanobacteria constitute important source for novel toxins that may be useful in mammalian
signalling pathways of apoptosis and platelet formation (Selheim
et al
., 2005).
vii) Genotoxicity studies
:
Ames
Salmonella
assay (strains TA98, TA100, TA102) and
Bacillus subtilis
multigene sporulation test (using 168 and
hcr-9
strains) were used to detect mutagenic response for
purifi ed toxins that proved to be negative (Grabow
et al
., 1982; Repavich
et al
., 1990). However, point
mutations were induced by MC-LR in four strains of
Salmonella typhimurium
by Ames test (Ding
et
al
., 1999). A genotoxic effect by MC-LR has been shown in
E
.
coli
(strain PQ37) (Mankiewicz
et al
.,
2002). Though point mutations were not induced, there was loss of heterozygosity when human
lymphoblastoid TK6 cells were treated with MC-LR (Zhan
et al
., 2004). MC-LR caused DNA damage in
mouse embryo fi broblasts and BHK-21 cell lines (Rao
et al
., 1998) as well as in cultured rat hepatocytes
(Ding
et al
., 1999). By employing Comet assay, Zegura
et al
. (2003) demonstrated MC-LR-induced
DNA strand breaks in human hepatoma HepG2 cells. But these DNA strand breaks have now been
attributed to early stages of apoptosis and not due to MC-LR-induced genotoxicity (Lankoff
et al
.,
2004). Moreover, Lankoff
et al
. (2003) reported that MC-LR did not cause any chromosomal damage
