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Several quinazoline derivatives have been found to possess a broad spectrum of biological activities. Previously our research group has synthesized and studied the anti-proliferative effects of N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine (DMQA). The current study evaluated the cytotoxic and apoptotic properties of DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A 549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's). Preliminary data revealed that the highest cytotoxic activity was against THP-1 leukemia cell line (IC50=0.66 μg/ml). The apoptotic properties of DMQA on THP-1 cells were characterized by change in nuclear morphology, DNA fragmentation, reduction of pro-caspases-3, 9, Bax/Bcl-2 levels, cleavage of poly (ADP-ribose) polymerase and cytosolic release of cytochrome c. Further investigation revealed a sub-G1 peak, phosphatidyl serine exposure and loss of mitochondrial membrane potential (MMP) in THP-1 cells. The role of caspases was crucial and was demonstrated by the inhibitors Z-VAD-FMK and Z-DEVD-FMK. Moreover DMQA was markedly less effective in inhibiting the growth of normal cells (PBMC's, IC50 =62.17 μg/ml). Based on the results we suggest that DMQA induced apoptosis via intrinsic pathway and could be a promising anticancer agent.

The freshwater protozoan ciliate, Paramecium caudatum was used in order to assess the potential cytotoxic effects of fenthion, an organophosphorus insecticide (OPI). It was found that fenthion at concentrations of 76 mg L � 1 (LC50 for 2 h) effected cellular morphology of P. caudatum and inhibited its locomotion, as well as degradation of cytoskeleton leading to cell destruction. Cytoskeleton morphology, cytoplasmic components and locomotor behaviour tests were performed by combined conventional light microscopy and a computerized video-tracking system. After short reparation periods from 10 min to 2 h, there was an increase in the number of apoptotic cells with typical features like plasma membrane blebbing, blackening of cytoplasm (due to mixing of the vacuolar contents) and outflow of cytoplasmic contents into blebs leading to cell lysis. The present findings on blackening of cytoplasm, multiple blebs and macronuclear changes indicate a possible apoptotic effect of fenthion on P. caudatum. Development of such simple apoptotic model systems like paramecium with simplicity in handling, low cost, ease in maintenance, rapid performance and high reproducibility provides an ‘early warning system’ for risk assessment in forecasting long-term hazards of pesticides on non-target organisms including humans. 2008 Elsevier Inc. All rights reserved.

The toxic effects of an organophosphorous insecticide, monochrotophos (MCP) were investigated on Paramecium caudatum in static acute toxicity tests (10 min and 2 h). The lethal concentrations (50%) were determined by probit method, for technical monocrotophos as 60 and 40.6 mg L−1, respectively. We have combined conventional light microscopy and a computerized video tracking system to determine behavioural and morphological changes in paramecium on exposure to MCP. Paramecia exposed to highest concentrations (90–100 mg L−1) used for 10 min exposure, exhibited initial increase with subsequent decrease in mobility with enormous blebbing, leading to lysis of cells. In the second set of experiments, the cells exposed to lethal concentration (40.6 mg L−1) for 2 h were under stress, and reduced their locomotor behaviour, i.e. distance travelled per unit time (mm in 6 min) and swimming speed (mm s−1) with increased time of exposure. In the third set of experiments, the number of generations and generation time i...

The continuous increase in the number of new chemicals as well as the discharges of solid and liquid wastes triggered the need for simple and inexpensive bioassays for routine testing. In recent years, there has been increasing development of methods (particularly rapid tests) for testing environmental samples. This paper describes the quick toxic evaluation of an organophosphorus insecticide, acephate ( O , S -dimethyl acetylphosphoramidothioate) on Paramecium caudatum for acute and sub-acute toxicity studies with reference to morphology, behaviour, and its generation time. The lethal concentrations for 10 min and 2 h were determined by probit method, as 500 mg L −1 and 300 mg L −1 , respectively. Higher concentrations of 10 min exposure caused cell lysis with disintegration of cell membrane and precipitation of protoplasm. Combination of conventional light microscopy and computerized video tracking systems were used to study the locomotor behaviour of paramecia. The test organism was under stress and exhibited an initial increase and subsequent decrease in the swimming speed when exposed to 1/4, 1/2, 3/4, and LC 50 concentrations for 10 min (125, 250, 375, and 500 mg L −1 , respectively). Similar changes were also noticed when paramecia were exposed to LC 50 for 2 h. In a separate set of experiments, the number of generations and generation time in 24 h was evaluated with respect to the different sub-lethal concentrations (30, 60, 120, and 240 mg L −1 ). The number of generations decreased and generation time extended significantly in a concentration dependent manner. The results indicate that the Paramecium toxicity assay could be used as a complimentary system to rapidly elucidate the cytotoxic potential of insecticides. The major advantages associated with these tests are: they are inexpensive, simple, user-friendly, space saving, and seem to be attractive alternatives to conventional bioassays.