In vitro and in vivo cytogenetic effects of recombinant human erythropoietin on the frequency of sister chromatid exchanges alone or in combination with mitomycin C.

BACKGROUND: Erythropoietin (EPO) is a glycoprotein which has a main property, erythropoiesis, but its range of action in the human body is very wide. It has been suggested that EPO acts cytoprotectively for many cell lines against many toxic causes in vitro and in vivo. Our aim was to study the action of EPO on DNA of two cell types, human lymphocytes in vitro and on P388 ascites tumor cells inoculated in BDF1 mice in the presence and absence of the genotoxic agent mitomycin C (MMC). METHOD: The sister chromatid exchange (SCE) assay was used as it is a very sensitive, simple and rapid method for detecting DNA damage. Proliferation rate indices (PRI) and mitotic indices (MI) were also counted. RESULTS: EPO did not alter the SCE level when it acted alone on both cell lines. MMC as a potent genotoxic agent increased SCE levels in vitro and in vivo. EPO used in combination with MMC significantly decreased SCE levels and increased PRI and MI values induced by MMC alone both in vitro and in vivo. CONCLUSIONS: EPO acts protectively against the genotoxic potential of MMC, and this action may have clinical implications.

Prognostic and predictive factors of invasive ductal breast carcinomas.

PURPOSE: To investigate the significance of certain immunohistochemical markers, namely estrogen (ER) and progesterone receptors (PgR), c-erbB-2 oncogene, p53 tumor suppressor gene and E-cadherin adhesion molecule, in invasive ductal breast carcinomas. METHODS: A series of 102 primary breast carcinomas of the ductal type and a standard immunohistochemical technique was used to detect the aforementioned biological markers. The findings were related to various clinical and pathological tumor characteristics, including lymph node metastases. RESULTS: ER and E-cadherin were expressed more commonly in tumors of low histological grade and small number (< or =3) of metastatic lymph nodes, whereas c-erbB-2 and the p53 gene were usually expressed in breast tumors of high histological grade and increased number (>3) of metastatic lymph nodes. PgR, on the other hand, was detected frequently in patients with early menarche and metastases in <3 lymph nodes, but this tendency was not statistically significant. CONCLUSION: The use of these biomarkers, preferably in combination, may provide additional prognostic and therapeutic information which may be proved useful in planning breast cancer treatment.

A combined biochemical and cytogenetic study of thioridazine-induced damage to nucleic acids.

In this work the biochemical effects of thioridazine, a commonly used phenothiazine, have been studied upon native double- and single-stranded DNA and also upon a supercoiled plasmid. The results indicate that thioridazine causes damage and scissions to these nucleic acids but only at concentrations much higher than the one used in our cytogenetic experiments and that the damage seems to depend on the concentrations used. Furthermore, we studied the action of thioridazine alone or in combination with caffeine and/or melphalan upon human lymphocytes in vitro. Thioridazine and caffeine (a well-known inhibitor of cellular repair mechanisms) were shown to act synergistically to potentiate the cytogenetic effect of melphalan on human lymphocytes. It is suggested that thioridazine alone or in combination with caffeine may exert its synergistic effect on melphalan cytotoxicity to cultured human lymphocytes not only indirectly, i.e. as a strong calmodulin inhibitor by facilitating the intracellular retention of melphalan, but also directly by reaction with nucleic acids and by causing scissions in and damage to them. Therefore, thioridazine (as chlorpromazine) has some potential as an adjuvant chemotherapeutic agent for the treatment of human cancer.