RESUMEN
In the present study, we used the method involving HPLC pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection for the determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in human urine. The mean levels of 8-oxoGua and 8-oxodGuo in the urine samples of the subjects on unrestricted diet were respectively 1.87 nmol/kg 24 h (+/-0.90) and 0.83 nmol/kg 24 h (+/-0.49), and in the case of the groups studied, they did not depend on the applied diet. The sum of the amounts of both compounds in urine can give information about the formation rate of 8-oxoGua in cellular DNA. It is also likely that the levels of modified nucleo-base/side in urine sample are reflective of the involvement of different repair pathways responsible for the removal of 8-oxodGuo from DNA, namely base excision repair (BER) and nucleotide excision repair (NER).
Asunto(s)
ADN/química , Desoxiguanosina/orina , Dieta , Guanina/análogos & derivados , Guanina/orina , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Calibración , Cromatografía Líquida de Alta Presión , Reparación del ADN , Desoxiguanosina/análogos & derivados , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Ácidos Nucleicos/metabolismoRESUMEN
The results of this work show a higher level of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a typical biomarker of oxidative stress, in uterine myoma tissues than in their respective tumor-free tissues. The level of this modified base was elevated in uterine tissues of premenopausal women when compared with postmenopausal ones. We have also found the correlation between the size of the tumor and the amount of 8-OH-dG. These results suggest that estrogen-produced 8-OH-dG may be one of the factors responsible for the formation of the myoma, and it may contribute to malignant transformation of myoma cells.
Asunto(s)
Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Leiomioma/química , Estrés Oxidativo , Neoplasias Uterinas/química , Útero/química , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Biomarcadores/análisis , Femenino , Humanos , Leiomioma/patología , Persona de Mediana Edad , Posmenopausia , Premenopausia , Valores de Referencia , Neoplasias Uterinas/patologíaRESUMEN
In the present study we measured the amount of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA isolated from lymphocytes of arteriosclerotic patients undergoing ozonetherapy. Treatment of the patients with therapeutic concentration of ozone caused a significant increase over the control value in the amount of 8-oxo-dG of DNA isolated from their lymphocytes. However, only three out of six patients examined responded positively to the treatment in terms of the base damage. The increases varied among patients, and were in the range of 100-450%. This interindividual difference may at least be partly explained by recently demonstrated heritable susceptibility to ozone.
Asunto(s)
Daño del ADN/efectos de los fármacos , Desoxiguanosina/análogos & derivados , Ozono/efectos adversos , 8-Hidroxi-2'-Desoxicoguanosina , Anciano , Arteriosclerosis/terapia , Desoxiguanosina/análisis , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Estrés Oxidativo/genéticaRESUMEN
This aim of this study was to measure the typical free radical-induced products of DNA bases in cellular DNA of cervical cancer tissues directly irradiated by applying brachytherapy to the patients. Significant increases in the amounts of modified bases over the control level were observed in the samples isolated after irradiation for all patients. These increases differed among patients and among products. The repair capacity and/or the amount of hypoxic cells inside the tumor may account for the different levels of modified bases. It is possible that the observed variabilities may account for the differences in clinical responses to brachytherapy.
Asunto(s)
Braquiterapia/efectos adversos , Daño del ADN , ADN de Neoplasias/efectos de la radiación , Adenina/análogos & derivados , Adenina/química , Adenina/metabolismo , Adenina/efectos de la radiación , Citosina/análogos & derivados , Citosina/química , Citosina/metabolismo , Citosina/efectos de la radiación , ADN de Neoplasias/química , ADN de Neoplasias/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Guanina/análogos & derivados , Guanina/química , Guanina/metabolismo , Guanina/efectos de la radiación , Humanos , Oxidación-Reducción , Pirimidinas/química , Pirimidinas/metabolismo , Pirimidinas/efectos de la radiación , Uracilo/análogos & derivados , Uracilo/química , Uracilo/metabolismo , Uracilo/efectos de la radiación , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
Anthracycline derivatives have been widely used in the treatment of several types of human malignancies. Cytotoxicity of these drugs has been attributed to inhibition of topoisomerase II as well as intracellular production of free radicals. In our work we used a gas chromatography/mass spectrometry technique to study free radical-induced DNA base modifications in chromatin isolated from lymphocytes of cancer patients who received chemotherapy with epirubicin (one of anthracycline's antitumor derivatives). The anticancer therapy caused significant increases in the amount of all four DNA base modifications over control levels in the lymphocytes of most of the patients. For the majority of the cases the base products returned to the control value 24 hr after the infusion of the drug, which suggests the removal of these lesions by cellular repair processes. However, some of the modified bases escaped repair. Because part of these modifications may possess premutagenic properties, they may be responsible for secondary cancers induced by chemotherapy.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Daño del ADN , Reparación del ADN/genética , ADN de Neoplasias/efectos de los fármacos , Epirrubicina/farmacología , Neoplasias/genética , Adulto , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapéutico , Cromatina/efectos de los fármacos , Cromatina/genética , Cromatina/aislamiento & purificación , Cromatina/metabolismo , ADN de Neoplasias/genética , Epirrubicina/química , Epirrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológicoRESUMEN
The objective of this study was to test the hypothesis that prostatic cancer is associated with the changes of zinc (Zn) and cadmium (Cd) concentration. Normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCA) were analyzed for Zn and Cd by atomic absorption spectrometry. Cd level was measured using a graphite furnace and Zn level was measured by flame mode. Metal content was assessed in whole tissues and in nuclear, plasma membrane, and cytosolic fractions. An increase of Zn content in BPH, but a decrease in PCA as compared to normal tissue, was observed. Cd concentration appeared to be higher in BPH and PCA than in normal tissue. No correlation between Zn and Cd level was found in BPH specimens obtained from the same patients. Probability values of p < or = 0.05 were considered to indicate significant differences. Obtained results seem to support the hypothesis of Cd carcinogenicity and preventing function of Zn in prostatic cancer. Plasma membrane fraction corresponding to lysosomal, mitochondrial, and microsomal subcellular compartments are probably critical in Zn and Cd participation in human prostate neoplasms.
Asunto(s)
Cadmio/metabolismo , Neoplasias de la Próstata/metabolismo , Zinc/metabolismo , Humanos , Masculino , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Fracciones Subcelulares/metabolismoRESUMEN
We investigated DNA base damage in genomic DNA of lymphocytes of cancer patients undergoing radiation therapy. Lymphocyte chromatin samples were analyzed by gas chromatography/isotope-dilution mass spectrometry for DNA base damage. The results provided evidence for formation of typical hydroxyl radical-induced base modifications in genomic DNA of lymphocytes. Different levels of DNA products in individuals were observed and, in the case of some patients, there was no significant product formation, possibly resulting from differences between individuals and between the types of radiation exposures. Decreases in product levels after an initial increase by radiation exposure were observed. This may indicate the removal of modified bases from lymphocyte DNA by cellular repair.
Asunto(s)
Daño del ADN , ADN/efectos de la radiación , Linfocitos/efectos de la radiación , Neoplasias/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/efectos adversosRESUMEN
The authors have studied DNA base damage and activities of antioxidant enzymes in human benign prostatic hyperplasia (BPH) tissues and surrounding disease-free tissues removed from prostate glands of 15 patients. In these tissues, endogenous levels of various typical hydroxyl radical-induced products of DNA bases and activities of catalase and superoxide dismutase were measured. The majority of patients had higher levels of DNA base lesions and lower activities of enzymes in BPH tissues than in normal prostate tissues. When activities of both enzymes were lower in BPH tissues than in normal tissues, the increases in the amounts of DNA base lesions over control levels were most prominent. In the case of similar enzyme activities in both BPH and normal tissues, no changes in levels of DNA base lesions were observed. These results suggest a possible association between antioxidant enzyme activities and levels of DNA base lesions in BPH tissues. Some of the identified DNA lesions are known to be premutagenic and may play a role in carcinogenesis. Although a possible link between BPH and prostate cancer is controversial, BPH patients with both decreased antioxidant enzyme activities and increased levels of DNA lesions may be at risk of developing prostate cancer.