Changes in activities of caspase-8 and caspase-9 in human cervical malignancy.

INTRODUCTION: The apoptotic process of programmed cell death and its dysfunctions in a variety of human diseases, including cervical cancer, has become the focus of extensive scientific research. Caspases are considered key factors in the execution of apoptosis, although there are many aspects of their role to be elucidated. It has been found that disturbance of initiator caspase-8 and caspase-9 expression or function may contribute to cancer formation/progression, and inactivation of them could promote resistance to current treatment approaches. In our research, the activities of caspase-8 and caspase-9 have been estimated during the progression of human cervical malignancy. MATERIALS AND METHODS: The experimental material includes human cervical tissue samples (normal and pathological), in which enzyme activities have been measured colorimetrically. RESULTS: Activities of caspase-8 and caspase-9 presented the highest increase, compared to the controls, in the low-grade squamous intraepithelial lesion samples (statistically significant, P < 0.01 by t test). The activities diminished in the high-grade squamous intraepithelial lesion and even more in the cancer samples but remained higher than the controls. CONCLUSION: The observed changes in the activities of caspase-8 and caspase-9 could be attributed to their involvement in the cervical tissue's effort to resist malignancy progression.

Cytogenetic activity of diazepam in normal human lymphocyte cultures.

INTRODUCTION: Diazepam (DZ) belongs to benzodiazepines, a group of drugs used for sedation, for the relief of anxiety, and in the treatment of epilepsy. It has been found that DZ influences cytotoxic activity and diminishes antiviral and antitumor reactions in human natural killer cells in vitro. It has also been demonstrated that DZ causes a significant increase in the frequency of chromosomal aberrations in human lymphocytes in vitro. MATERIALS AND METHODS: In the present research the cytogenetic effects of DZ have been studied in normal human lymphocyte cultures of peripheral blood at 17.6-211.2 microM (final concentrations). Sister chromatid exchanges (SCEs), one of the most sensitive methods reflecting instability in DNA or a deficiency in DNA repair mechanisms, and proliferation rate index (PRI), a valuable indicator for cytostatic activity, have been evaluated. RESULTS: After 72-h incubation, DZ was found to cause a dose-dependent, statistically significant increase of SCE frequency (p < 0.001), followed by an equally significant decrease of PRI (p < 0.001). CONCLUSION: Our results suggest that DZ's administration presents cytogenetic effects in normal human lymphocyte cultures.