Abstract <p>We conducted the experiments of the short-term (1 h) testing effect of the herbicide paraquat, one of the strongest inducers of oxidative stress, on cultured blood cells (late G₁ stage of the first mitosis, 4 × 10^–8 mol/L) of nine healthy donors. In 60-h (short-term) and 120-h (long-term) lymphocyte cultures exposed to paraquat in vitro, the average frequencies of aberrant cells were 4.05 ± 0.55 and 9.42 ± 1.23%, respectively, which significantly exceed the corresponding control levels of 1.16 ± 0.30 and 1.70 ± 0.50% (<i>p</i> = 0.008 and 0.018, respectively). The observed genotoxic effects are primarily due to the induction of simple chromatid aberrations (single fragments), the levels of which were 3.32 ± 0.40 and 8.92 ± 1.40 per 100 cells as a result of short-term and long-term lymphocyte cultivation, respectively (in comparison with 1.03 ± 0.34 and 1.56 ± 0.38 per 100 cells in the corresponding control). The frequencies of paired chromosomal fragments in cell cultures of both types also significantly (or on the trend level) exceeded the control frequencies (<i>p</i> = 0.046 and 0.068 for 60- and 120-h cultures, respectively). No differences were found between 60- and 120-h unexposed cell cultures in the level of aberrant cells and chromosome aberrations of all types. In contrast, the long-term lymphocyte cultures exposed to paraquat demonstrated significantly increased levels of aberrant metaphases and single chromatid fragments compared to short-term exposed cultures (<i>p</i> = 0.001). The long-term effects were shown to be characterized by higher individual values of Cohen’s omega (w), from 0.157 to 0.259, compared to those for 60-h cultures, from 0.057 to 0.153. The data indicate the induction of genomic instability in distant descendants of human lymphocytes exposed to short-term paraquat at the beginning of cultivation, and its individual nature.</p>