Apoptotic versus genotoxic potential of anti-tumor agents: a concept of duality in unity.

Recent advances in anti-tumor therapy have raised a problem of secondary tumors and tumor resistance. Secondary tumors induced by chemotherapeutic agents as a consequence of primary therapy have poor prognostic outcome. Many new insights into molecular controls of cell cycle progression of normal and cancer cells can provide a useful framework in order to identify potential targets for anti-tumor therapies. One of the most promising strategies is the possibility to modulate apoptosis induced by anti-tumor agents. Cancer cell survival after chemotherapy will depend on specific checkpoints and/or repair pathways that have been lost, leading either to greater susceptibility to anti-tumor agents when the repair of damage is most important for survival or to greater resistance when the apoptotic response is more important. We have proposed a hypothesis that views survival and apoptotic processes (duality) in normal and tumor cells as genetically coupled (unity). We introduce, through a theoretical background, a new pathway of apoptotic inhibition. The proposed process of apoptotic inhibition is induced by mutation fixation in which recombination/repair processes (hRAD genes) play an important role. These coupled processes (duality in unity), to our view, underline tumor resistance by apoptotic inhibition and mutation fixation in normal cells exposed to anti-tumor agents.

Immunosuppressive and cytogenetic effects of pelvic irradiation on the peripheral lymphocytes of patients with cervical cancer. One year follow-up.

The circulating lymphocytes of patients treated for cervical cancer were examined by four independent manners: by evaluation of T-cell proportion in peripheral blood, proliferative response upon PHA stimulation, PHA-induced leukocyte migration inhibition, and by concomitant chromosome aberration frequency. The immediate and longer-term effects of pelvic irradiation on T lymphocytes were investigated in 19 patients prior to, during, and immediately after radiotherapy, and then at subsequent intervals of two, three and five months. Radiotherapy caused profound depression of already diminished T-cell number and their proliferative response; both parameters gradually recovered during post-treatment period, and achieved their pretreatment values at the end of follow-up. The leukocyte migration inhibition was much less affected; it slightly deteriorated in the middle of post-treatment period, but reached the pretreatment level at the end of monitoring. The chromosome aberration frequency increased during irradiation in dose-dependent manner; it decreased gradually thereafter, but remained high during follow-up. Their elimination rate correlated with the recovery of T-cell number and proliferative response. However, at the end of monitoring, when all immunological parameters were completely recovered from harmful effect of irradiation, the percentage of chromosome aberrations remained high (12.5%), although significantly lower than the post-treatment one.