## 3 Results and Discussion
### Genotoxicity and Cytotoxicity Biomarkers
#### 3.2.2 Mitotic Index and Proliferation Index  
An increase or decrease in the MI can determine cytotoxicity levels induced by exposure to a wide range of compounds. An MI study of KD and SD on in vitro lymphocyte cultures was performed in a total of 500 cells for each experiment. Data concerning the MI are summarised in Table 3. Lymphocytes cultured in the presence of 50, 400, and 800 \(\rm\mu g/mL\) of KD exhibited a similar MI to those recorded in lymphocytes without the fruit extracts (control) and with solvent (solvent control). However, a significant decrease (\(p<0.05\)) in MI was observed in cultures treated with 800 \(\rm\mu g/mL\) of SD. In addition, other natural extracts have demonstrated cytotoxic activity against human cells in vitro [11; 45]. The observed decrease in mitotic activity could be attributed to various factors, such as the interruption of the mitotic cell cycle during interphase, inhibition of crucial nuclear protein synthesis required for normal mitotic progression, or suppression of DNA synthesis [46]. Data concerning the PI of KD and SD in lymphocytes are summarised in Table 3. Lymphocyte cultures treated only with the solvent or with the different concentrations of KD and SD showed PI values similar to the control value (\(p>0.05\)). Therefore, it can be concluded that these extracts do not exhibit cytostatic effects on human peripheral blood lymphocytes in in vitro cultures and, consequently, are not genotoxic. Other natural extracts have also shown results similar to our in vitro study of PI [45]. \begin{table}
\begin{tabular}{l c c c c} \hline
**Conditions** & **Y\({}_{\rm SCE}\)** & **Y\({}_{\rm 1 SCE}\)** & **Y\({}_{\rm 2 SCE}\)** & **Y\({}_{\rm 3 SCE}\)** \\ \hline
0 (control) & 8.0 \(\pm\) 0.5 & 7.2 \(\pm\) 0.4 & 0.32 \(\pm\) 0.08 & 0.06 \(\pm\) 0.03 \\
0 + methanol/water 70:30 & 8.2 \(\pm\) 0.5 & 6.5 \(\pm\) 0.4 & 0.86 \(\pm\) 0.13 & 0.00 \(\pm\) 0.00 \\ (control + solvent) & & & & \\ \hline KD 50 & 7.5 \(\pm\) 0.4 & 6.0 \(\pm\) 0.3 & 0.66 \(\pm\) 0.11 * & 0.06 \(\pm\) 0.03 * \\ KD 400 & 7.8 \(\pm\) 0.5 & 7.0 \(\pm\) 0.4 & 0.32 \(\pm\) 0.08 * & 0.04 \(\pm\) 0.03 * \\ KD 800 & 7.8 \(\pm\) 0.5 & 6.3 \(\pm\) 0.3 & 0.60 \(\pm\) 0.11 * & 0.10 \(\pm\) 0.04 * \\ \hline SD 50 & 6.4 \(\pm\) 0.3 & 5.4 \(\pm\)0.3 * & 0.48 \(\pm\) 0.10 * & 0.02 \(\pm\) 0.02 * \\ SD 400 & 6.4 \(\pm\) 0.5 & 5.5 \(\pm\) 0.5 * & 0.48 \(\pm\) 0.14 * & 0.00 \(\pm\) 0.00 * \\ SD 800 & 5.3 \(\pm\) 0.3 * & 4.8 \(\pm\) 0.3 * & 0.26 \(\pm\) 0.08 * & 0.00 \(\pm\) 0.00 * \\ \hline \end{tabular}  
* Results are expressed as means \(\pm\) standard errors.
* The difference was statistically significant (\(p<0.05\)).  
\end{table} 
Table 2: The frequency of sister chromatid exchange (Y\({}_{\rm SCE}\)) in human lymphocytes exposed to methanol/water (70:30 \(v/v\)) and different concentrations of freeze-dried kiwifruit (KD) and strawberry (SD) extracts (50, 400, and 800 \(\rm\mu g/mL\)) and frequencies of chromosomes with one (Y\({}_{\rm 1 SCE}\)), two (Y\({}_{\rm 2 SCE}\)), or three (Y\({}_{\rm 3 SCE}\)) sister chromatid exchanges assessed in a total of 50 cells. The relative indexes RMI and PRI were similar to the control (\(p>0.05\)) (Table 3). Studies examining the relationship between SCE actions and various expressions of cytotoxicity have indicated that an increase in SCE frequency is often accompanied by decreased cell survival and alterations in cell cycle kinetics, resulting in lower values of the mitotic index (MI) [47]. In preclinical screening of natural products for potential antitumor activity, it is common to evaluate a single parameter, typically cell death. However, more comprehensive information can be obtained by assessing two biological endpoints, such as the MI and proliferation index (PI) assays [30]. For example, a reduction in the MI can indicate cell death or arrest of the cell cycle at any stage during interphase.