Comparative study of two evaluation methods for the genotoxic effects of environmental heavy metals on normal cells.

Genetic modifications caused by chronic exposure to low levels of toxic metals may activate stress-signaling pathways, thus increasing cancer incidence among affected individuals. The aim of this study was to evaluate the relationship between exposure to heavy metals and the incidence of chromosomal aberrations and DNA lesions in a chronically exposed population by using specific biomarkers. The study included 156 subjects divided into two major groups: exposed individuals (in a heavy metal contaminated region, Maramures, Romania) and non-exposed population, as control group (Cluj, Romania). We compared the results of two cytogenetic methods for the detection and quantification of DNA lesions and chromosomal aberrations in normal human cells: Single Cell Gel Electrophoresis or Comet assay and Cytokinesis Block Micronucleus assay. The methods were performed on lymphocytes isolated from whole blood in density gradient. The basal DNA lesions and chromosomal aberrations were evaluated, as well as the repair capacity of the supplementary lesions induced by genotoxic agents such as ionizing radiations. Our results showed a great interindividual variability in the basal level of the DNA lesions and chromosomal aberrations, between and within the groups, the most affected being the heavy metals-exposed groups. Non-exposed subjects from rural area Cluj appeared to be more susceptible to the induction of supplementary DNA lesions and chromosomal aberrations by irradiation. The most efficient repair capacity of the radio-induced DNA lesions was observed in the non-exposed Cluj urban group. Both cytogenetic assays (as tools for detection of DNA lesions and chromosomal aberrations) may be used in human biomonitoring studies as indicators of early biological effects induced by exposure to heavy metals.

Clinical results of medium dose rate brachytherapy combined with external beam radiotherapy in the treatment of advanced cervical carcinoma.

PURPOSE: To evaluate the overall and disease-free survival of patients with advanced cervical carcinoma (FIGO stages IIB-IIIB) treated with external beam radiotherapy (EBRT) and medium dose rate brachytherapy (MDR-BT) plus/minus surgery. PATIENTS AND METHODS: One hundred and seven patients received preoperative RT (group A) and 154 were treated with definitive RT (group B); 73 patients in both groups also received cisplatin as radiosensitizer. EBRT delivered as preoperative reached a total dose of 44-46 Gy/pelvis, whereas the definitive RT reached a total dose of 62-64 Gy with standard fractionation. MDR-BT was performed with a LDR/MDR Cs-137 Selectron machine; 10 Gy/point A were delivered in the preoperative group A and 14 Gy/point A/, 1-2 fractions in group B. Cisplatin as radiosensitizer was administered during EBRT at a dose of 20 mg/m(2)/day for 5 days with 21 days interval between cycles. RESULTS: With a median follow-up of 44.4 months (range 3.4-61.6) the overall survival at 3 years in group A was 92% vs. 68% for group B (p<0.01). According to FIGO stages 3-year overall survival was 88% in stage IIB, 79% in IIIA and 60% in IIIB (p<0.01). Three-year local control was 73.5% (192 patients). Thirty-three (13%) patients developed locoregional recurrences, and another 8 (3.07%) locoregional recurrences plus distant metastases. CONCLUSION: The association of EBRT with MDR-BT represents an effective treatment in advanced cervical carcinoma. A significant difference in 3-year overall survival was found, favoring preoperative RT, with a very good rate of local control.