Comments on the paper by E. M. Minicucci et al. “DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy”

Abstract

I read the paper by Minicucci et al. ‘‘DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy’’ [1] with great interest because recently I analyzed all available literature sources concerning the influence of chemoand radiotherapies on exfoliated mucosal cells [2]. The problem of possible micronuclei (MN)-inducing activity of antiblastics on epithelial oral mucosa cells has not been studied well. Only four papers were published concerning cancer patients (for review see [2]) and two concerning patients with other diseases treated with cytostatics [3, 4]. It has been shown that in these papers positive effect was registered in some cases. But no firm conclusion could be drawn if chemotherapy induces MN in oral epithelial cells. I think it is because all investigators applied various time points to collect exfoliated epithelial cells after the application of cytostatics. For example, it is practically not clear when the samples of buccal cells were collected by Minicucci et al. [1]. The time factor could play a key role in finding of MN because of kinetics (or the life cycle) of these types of cells. According to Szete et al. [5], the half-life of buccal cells is about 15 days and Kassie et al. [6] showed that MN level is highest 28 days after the effect of mutagen. After that there is an elimination of cells with MN. Hence, collection of oral cells ought to be done not later than 30 days after the last application of cytostatic drug. In my opinion, success of such kind of investigations depends mainly on the study of primary patients (without any treatment which can induce damage of cytogenetic structures) after one cycle of chemotherapy because it is mostly toxic for organism, and it could induce changes in basal cell kinetics. Also, due to this the so-called nuclear anomalies (karyolysis, karyorrhexis, pycnosis) can appear [7]. The evaluation of the so-called nuclear anomalies along with MN will improve the quality of the studies. Minicucci et al. [1] found significantly increased levels of MN in lymphocytes which were collected at the same time as exfoliated cells. It is because, unlike epithelial cells, half-life of lymphocytes is substantially longer (some years) that it is possible to find an increased number of MN in lymphocytes of children under therapy of much longer time than 30 days (the critical time point to register MN in epithelial cells) [8]. It is noteworthy that Torres-Bugarin et al. [7] investigated about 40 patients under antiblastic therapy, and found significantly increased levels of MN in some of them. But among them were subjects after two or even three cycles of therapy. Like Minicucci et al. [1], no firm information was presented as to when the buccal cells were collected. Based on the data presented by the authors, the number of cells with MN only in primary cancer patients treated with three chemotherapeutic schedules was calculated. Totally among them 19 were primary, and MN frequencies were 1.6 ± 0.4% before and 2.6 ± 0.7% after treatment (p [ 0.05, Mann–Whitney test). In ten patients treated with carboplatin ?5-fluorouracil MN numbers were 0.95 ± 0.12% before and 1.35 ± 0.42% after treatment, and in nine patients treated with isophosphamide ? epirubicin the frequencies were 2.9 ± 1.0% (before) and 4.9 ± 1.6% (after treatment) (p [ 0.05 in both cases, Mann–Whitney U test). As can be noted, no significant increase of cells with MN was found also in primary patients after one course of therapy. But the time of cell collection was not clearly indicated by the authors [1]. Ramos-Remus studied and A. Nersesyan (&) Institute of Cancer Research, Vienna, Austria e-mail: armen.nersesyan@meduniwien.ac.at