The Velika Morava River is the greatest national Serbian river and the significant tributary of the Danube River. The major problems in the Velika Morava River Basin (VMRB) represent untreated industrial and municipal wastewaters. In this study, the level of genotoxic potential at the sites along the VMRB was evaluated by parallel in vitro and in situ approach. Within in vitro testing, genotoxicity of native water samples collected from the sites in VMRB was evaluated by SOS/umuC test on Salmonella typhimurium TA1535/pSK1002 and by the comet assay on HepG2 cells. DNA damage in situ was assessed in bleak (Alburnus alburnus) erythrocytes by the comet (alkaline and Fpg-modified comet) and micronucleus assays. Additionally, the concentration of heavy metals in fish tissue was measured and this data, compiled with the data of the physico-chemical parameters measured in water, was used as a measure of the pollution pressure at the sites.

Results showed that applied in vitro tests with native water samples are less sensitive in comparison with in situ tests and should be taken with precaution when making predictions on the status of the ecosystem. Within applied battery of in situ assays differential sensitivity of assays was observed where alkaline comet assay showed the highest potential in differentiation of the sites based on genotoxic potential. Integrated biomarker response showed that usage of the battery of bioassays provides better insight in a genotoxic effects in animals, and consequently, that the holistic approach is more suitable for this type of study.

Velika Morava河是塞尔维亚最大的国家河流，是多瑙河的重要支流。Velika Morava流域（VMRB）的主要问题代表未经处理的工业和市政废水。在这项研究中，通过平行的体外和原位方法评估了VMRB沿线各部位的遗传毒性潜力。在体外测试中，通过在鼠伤寒沙门氏菌TA1535 / pSK1002上进行的SOS / umuC测试以及在HepG2细胞上进行的彗星分析，评估了从VMRB站点收集的天然水样品的遗传毒性。评估DNA的原位损伤暗淡（Alburnus alburnus）彗星（碱性和Fpg修饰的彗星）和微核测定法检测红细胞。此外，还测量了鱼组织中重金属的浓度，并将该数据与水中测得的理化参数数据汇总起来，作为该地点污染压力的量度。

结果表明，与原位测试相比，使用天然水样品进行的体外测试敏感性较低，在对生态系统的状态进行预测时应采取预防措施。在原位测定的应用电池组中，观察到了测定的灵敏度差异，其中碱彗星测定显示了基于遗传毒性潜力在位点分化方面具有最高的潜力。综合的生物标志物反应表明，使用一系列生物测定可以更好地了解动物的遗传毒性作用，因此，整体方法更适合此类研究。