Topotecan (TpT) is a major inhibitory compound of topoisomerase (topo) I that plays important roles in gene transcription and cell division. We have previously reported that heparin and heparan sulfate (HS) might be transported to the cell nucleus and they can interact with topoisomerase I. We hypothesized that heparin and HS might interfere with the action of TpT. To test this hypothesis we isolated topoisomerase I containing cell nuclear protein fractions from normal liver, liver cancer tissues, and hepatoma cell lines. The enzymatic activity of these extracts was measured in the presence of heparin, liver HS, and liver cancer HS. In addition, topo I activity, cell viability, and apoptosis of HepG2 and Hep3B cells were investigated after heparin and TpT treatments. Liver cancer HS inhibited topo I activity in vitro. Heparin treatment abrogated topo I enzyme activity in Hep3B cells, but not in HepG2 cells, where the basal activity was higher. Heparin protected the two hepatoma cell lines from TpT actions and decreased the rate of TpT induced S phase block and cell death. These results suggest that heparin and HS might interfere with the function of TpT in liver and liver cancer.

Hearing loss is the most common sensory deficit in humans. Early diagnosis and intervention are important in the acquisition of hearing, speech, and linguistic skills, thereby contributing to the positive development of the child. Aims:To study the state of hearing in children living in Kazakhstan, to identify the proportion of mutations in the connexin-26 gene in the event of sensorineural deafness.Methods: prospective case-control analysis. In total, 454 participants were examined.Results: It has been identified that for the Kazakh population with regard to the polymorphism of gene frequency GJB2 (35delG, 235Cdel, 167delT) the most characteristic is allele spectrum frequencies of 167delT polymorphism. Conclusion:Thus, the population frequencies of the mutation were studied: 35delG (0.49±0.28), 235delC (0.66±0.33), 167delT (1.64±0.51) of the GJB2 gene in the Kazakh population, which makes a significant contribution to the study of the gene pool of Kazakhs.