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ABSTRACTBackground: Pollution of aquatic ecosystems with heavy metals leads to decrease of the biodiversity and accumulation of toxicants in the food chain. Species of the genus Scenedesmus are sensitive indicators of environmental changes and have been used for the evaluation of risk factors for contamination of aquatic ecosystems. The microalga Scenedesmus incrassatulus can remove chromium and cadmium from the growth medium. Also, mammalian cell lines are another type of test system that has been used to study the mechanisms of heavy metal toxicity. However, little is known about the sensitivity and potential application of different human cell lines for bio-monitoring of heavy metal contamination. Aim: To investigate the toxicity of increasing concentrations of cadmium, nickel and lead on the green microalga Scenedesmus incrassatulus and the human cell lines HeLa, A549, FL, and Caco-2. Materials and Methods: To evaluate the toxic effects of Cd, Ni, and Pb, two test systems were used: an algal culture of S. incrassatulus and four human cell lines. For the algal system, the growth of the algae and the features such as "cell number in the coenobium/single cells", "position of the inner cells in the coenobium", and "shape of the peripheral cell", were assessed. For the human cell cultures, the methyl-thiazol-tetrazolium (MTT) and neutral red assays were performed. In both the systems, the effects were measured at different time points (24, 48, and 72 hours) of treatment. Results: The experimental observations showed that lead exposure in maximal permissible levels (MPL) inhibited the growth of the green algae S. incrassatulus, while cadmium had a stimulating effect even at lower test concentrations. Cadmium and nickel treatment affected the morphological features "cell number in the coenobium/single cells" and "position of the inner cells in the coenobium". Regarding "shape of the peripheral cell", lead had the most significant effect after 24 h of treatment, which was expressed in reduction of the type "incrassatulus" compared to the type "obliquus". Cytotoxic effects of the heavy metals were also observed for all tested human cell lines. HeLa, FL and Caco-2 were most sensitive to cadmium compared to lead, while A549 cells showed equal sensitivity to all three heavy metals. Conclusion: The reported data presented specific impacts on the studied parameters for both the test-systems. The present study concluded that the green alga S. incrassatulus could be used as an effective test system for the biomonitoring of lead pollution. The cell line A549 can serve as a sensitive test system for the presence of cadmium, nickel and lead.