RESUMEN
The aim of the study was to identify and quantify lymphocytes with asynchronous replication of the AURKA and TP53 genes in cancer patients versus controls and to assess the diagnostic capabilities of this approach. MATERIALS AND METHODS: The study was carried out with peripheral blood lymphocytes probed for the AURKA and TP53 genes using the interphase fluorescence in situ hybridization (FISH) method (Vysis, USA and Kreatech, The Netherlands). The control group included 70 people: clinically healthy donors and patients with non-oncological diseases such as gastritis, pancreatitis, chronic calculous cholecystitis, bronchial asthma, peptic ulcer disease, inguinal hernia, arthrosis, myoma, hepatitis, epilepsy, chronic prostatitis, chronic tonsillitis, and rectal adenoma. The group of cancer patients included 219 people with various oncological diseases: gastric cancer (n=68), colorectal cancer (n=30), chronic lymphocytic leukemia (n=52), Hodgkin lymphoma (n=33), and polyneoplasia (n=41). RESULTS: In the control group, the mean frequency of lymphocytes with asynchronous gene replication (AGR) was 22.0±3.4% for AURKA and 18.0±3.2% for TP53; in the group of cancer patients, that was 36.8±4.8 and 28.4±5.1%, respectively. The excessive presence of lymphocytes with the AGR in cancer patients was consistent and statistically significant (p<0.0001). For the AURKA gene, the AGR-based cancer detection showed a sensitivity of 98.6±0.7%, a specificity of 100%, and an accuracy of 98.3±0.8%, and for the TP53 gene - 78.6±3.1, 98.5±0.9, and 85.9±2.6%, respectively. CONCLUSION: This pilot study on lymphocytes with AGR of AURKA and TP53 genes in cancer patients can serve a basis for creating a new molecular cytogenetic technology for detecting malignant neoplasms in humans.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Replicación del ADN , Humanos , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/genética , Linfocitos/patología , Masculino , Proyectos Piloto , PronósticoRESUMEN
A study of frequency of unstable chromosome aberrations in 50 workers of nuclear chemical plants in remote period after beginning or finishing professional contact with ionizing radiation was carried out. 14 persons from this cohort were mainly whole-body exposed to external gamma-rays and 36 were exposed to combined external and internal radiation from incorporated Pu nuclides. In results of this irradiating practically every subject had a chronical radiation sickness. In the 1-st group the frequency of unstable aberrations varied from 0.2 to 3.6 per 100 cells and exceeded reliably control level in 5 persons. In the 2-nd group the frequency of unstable aberrations varied from 0 to 11.6 per 100 cells and exceeded reliably control level in 20 examined workers. The FISH study of frequency of stable aberrations was performed in 13 subjects who were exposed to combined external and internal radiation. Total frequency of complete and incomplete translocations varied from 0.6 to 18.5 aberrations per genome per 100 cells and reliable exceeded control level in 9 subjects. Non-random participation in exchange rearrangements (translocations) was revealed for used set of chromosomes (2, 3 and 8).
Asunto(s)
Aberraciones Cromosómicas , Mutación , Enfermedades Profesionales/genética , Exposición Profesional , Plutonio/efectos adversos , Centrales Eléctricas , Traumatismos por Radiación/etiología , Traumatismos por Radiación/genética , Adulto , Anciano , Inestabilidad Cromosómica , Cromosomas Humanos Par 2/efectos de la radiación , Cromosomas Humanos Par 3/efectos de la radiación , Cromosomas Humanos Par 8/efectos de la radiación , Estudios de Cohortes , Interpretación Estadística de Datos , Femenino , Estudios de Seguimiento , Rayos gamma , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Factores de Tiempo , Translocación GenéticaRESUMEN
Investigation of application of chromosome aberrations of lymphocytes in peripheral blood for biological dosimetry purposes in remote (up to 40 years) period after acute exposure to doses of 1 Gy and more was carried out. The comparative analysis of frequency of unstable and stable (using FISH and G-banding methods) aberrations was performed for 24 subjects accidentally exposed to radiation on nuclear submarines during 1961-1985. Statistically significant increasing of frequency of dicentrics and centric rings was determined in the exposed subjects in remote period after exposure to compare with controls. Their sum frequency in the exposed group varied depending on ARS heaviness from 0.1 to 1.0 aberrations per 100 cells. In control group it was from 0 to 0.2 correspondingly. Translocation frequency (complete + incomplete) fixed by FISH method (2, 4, and 12 chromosomes) varied within the limits of 0.2-16.0 for exposed subjects and 0.3-1.26 translocations per genome per 100 cells for controls. Some examined persons (5 subjects) exposed to accident in 1985 had results of analysis of unstable chromosome aberration in acute period after exposure that allow to estimate obtained doses by dicentrics frequency which having good correlation with ARS heaviness. Individual dosed using traslocation frequency were defined retrospectively in 11 from 21 exposed persons. They correlate with calculated physics doses and doses estimated by haematolotical parameters in acute period and also doses obtained by ESR spectroscopy of tooth enamel in remote period.