Assuntos
Endocardite/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/cirurgia , Desenho de Prótese/instrumentação , Reoperação/instrumentação , Endocardite/complicações , Endocardite/diagnóstico por imagem , Feminino , Próteses Valvulares Cardíacas/normas , Implante de Prótese de Valva Cardíaca/normas , Humanos , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Desenho de Prótese/normas , Reoperação/normasAssuntos
Anestesia em Procedimentos Cardíacos/tendências , Implante de Prótese de Valva Cardíaca/tendências , Desenho de Prótese/tendências , Procedimentos Cirúrgicos Vasculares/tendências , Anestesia em Procedimentos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/tendências , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Desenho de Prótese/métodos , Procedimentos Cirúrgicos Vasculares/métodosAssuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Assistência Perioperatória/métodos , Feocromocitoma/terapia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Veia Cava Inferior/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Veia Cava Inferior/patologiaRESUMO
Particulate hexavalent chromium [Cr(VI)] compounds are well-established human carcinogens. Cr(VI)-induced tumors are characterized by chromosomal instability (CIN); however, the mechanisms of this effect are unknown. We investigated the hypothesis that homologous recombination (HR) repair of DNA double-strand breaks protect cells from Cr(VI)-induced CIN by focusing on the XRCC3 and RAD51C genes, which play an important role in cellular resistance to DNA double-strand breaks. We used Chinese hamster cells defective in each HR gene (irs3 for RAD51C and irs1SF for XRCC3) and compared with their wildtype parental and cDNA-complemented controls. We found that the intracellular Cr ion levels varied among the cell lines after particulate chromate treatment. Importantly, accounting for differences in Cr ion levels, we discovered that XRCC3 and RAD51C cells treated with lead chromate had increased cytotoxicity and chromosomal aberrations, relative to wildtype and cDNA-complimented cells. We also observed the emergence of high levels of chromatid exchanges in the two mutant cell lines. For example, 1microg/cm(2) lead chromate induced 20 and 32 exchanges in XRCC3- and RAD51C-deficient cells, respectively, whereas no exchanges were detected in the wildtype and cDNA-complemented cells. These observations suggest that HR protects cells from Cr(VI)-induced CIN, consistent with the ability of particulate Cr(VI) to induce double-strand breaks.
Assuntos
Cromatos/toxicidade , Instabilidade Cromossômica/efeitos dos fármacos , Reparo do DNA , Chumbo/toxicidade , Recombinação Genética , Animais , Células CHO , Carcinógenos/toxicidade , Linhagem Celular , Cricetinae , Cricetulus , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Humanos , Rad51 Recombinase/deficiência , Rad51 Recombinase/genéticaRESUMO
Water-insoluble hexavalent chromium compounds are well-established human lung carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA damage, chromosome aberrations, and dose-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between lead chromate-induced DNA damage and chromosome aberrations is unknown. Our study focus was on examining the role of XRCC1 in lead chromate-induced cytotoxicity and structural chromosomal aberrations in CHO cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1 gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8 and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead chromate particles-induced cell death. The frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage changed dramatically. Chromatid and isochromatid lesions were the most prominent aberrations induced in all cell lines. XRCC1 was essential to reduce the formation of chromatid lesions but not for isochromatid lesions. In addition, XRCC1 deficiency resulted in a dramatic increase in the number of chromatid exchanges, indicating that XRCC1 is involved in protection from lead chromate-induced chromosome instability.
Assuntos
Cromatos/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Proteínas de Ligação a DNA/metabolismo , Chumbo/toxicidade , Animais , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cromo/análise , Cricetinae , Cricetulus , Proteínas de Ligação a DNA/deficiência , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Water-insoluble hexavalent chromium compounds are well-established human lung carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA damage, chromosome aberrations, and dose-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between lead chromate-induced DNA damage and chromosome aberrations is unknown. Our study focus was on examining the role of XRCC1 in lead chromate-induced cytotoxicity and structural chromosomal aberrations in CHO cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1 gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8 and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead chromate particles-induced cell death. The frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage changed dramatically. Chromatid and isochromatid lesions were the most prominent aberrations induced in all cell lines. XRCC1 was essential to reduce the formation of chromatid lesions, but not for isochromatid lesions. In addition, XRCC1 deficiency resulted in a dramatic increase in the number of chromatid exchanges, indicating that XRCC1 is involved in protection from lead chromate-induced chromosome instability.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cromatos/toxicidade , Aberrações Cromossômicas , Proteínas de Ligação a DNA/fisiologia , Animais , Células CHO , Cricetinae , Cricetulus , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Hexavalent chromium Cr(VI) is a well known human carcinogen. This genotoxic metal induces DNA strand breaks and chromosome damage. However, the relationship between these lesions is uncertain. Our study focused on examining the role of XRCC1 in sodium chromate-induced cytotoxicity and chromosomal aberrations in Chinese Hamster Ovary (CHO) cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant) and H9T3 (EM9 complemented with human XRCC1 gene). Results show that concentration-dependent decreases in relative survival are similar in all three cell lines, indicating that XRCC1 is not crucial for protecting cells from sodium chromate-induced cytotoxicity. Similarly the frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total number of Cr(VI)-induced chromosome aberrations was exacerbated by XRCC1 deficiency and the spectrum of chromosome damage changed dramatically. Specifically, chromatid and isochromatid lesions were the most prominent aberrations induced in the cell lines and XRCC1 was essential to reduce the formation of chromatid lesions. In addition, XRCC1 deficiency caused a dramatic increase in the number of chromatid exchanges indicating that it is involved in protection from Cr(VI)-induced chromosome instability.