背景与目的:进一步明确镉对人类细胞DNA的损伤效应以及对损伤修复的干扰作用。材料与方法:利用简化人全血细胞检测法研究了CdCl2诱导人全血细胞(主要是淋巴细胞和单核细胞参与反应)程序外:DNA合成(unscheduled DNA synthesis,UDS)的能...背景与目的:进一步明确镉对人类细胞DNA的损伤效应以及对损伤修复的干扰作用。材料与方法:利用简化人全血细胞检测法研究了CdCl2诱导人全血细胞(主要是淋巴细胞和单核细胞参与反应)程序外:DNA合成(unscheduled DNA synthesis,UDS)的能力及其对该细胞经N-甲基-N'-硝基-亚硝基胍(MNNG)或紫外线(UV)处理后DNA修复合成的影响。结果:0.1-10 μmol/L的CdCl2单独作用,细胞DNA修复合成前体物3H-TdR的掺入量与镉浓度量呈高度正相关的剂量-效应关系,其中10μmol／L剂量组与对照组相比差异有显著性;CdCl2在对人全血细胞UDS无明显诱导的剂量水平下即可使MNNG作用后DNA的修复合成受抑;与之相反,1μmol／L CdCl2与UV共同作用对人全血细胞UDS的诱导存在明显的协同作用。结论:较高浓度的镉对DNA具有损伤作用;而在较低浓度下,镉干扰DNA修复过程的作用较明显。上述直接和间接的遗传毒作用可能是镉致癌的机制之一。展开更多
Background: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is ...Background: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun-exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER-defective form of XP of seven complementation groups, designated XP-A to XP-G. These complementation groups correspond to different proteins involved in the NER process. XP-A classically includes some of the most severely affected patients. Objectives: We describe a 61-year-old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene. Methods: Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing. Results: Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP-A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A→ G at the eighth nucleotide of展开更多
文摘背景与目的:进一步明确镉对人类细胞DNA的损伤效应以及对损伤修复的干扰作用。材料与方法:利用简化人全血细胞检测法研究了CdCl2诱导人全血细胞(主要是淋巴细胞和单核细胞参与反应)程序外:DNA合成(unscheduled DNA synthesis,UDS)的能力及其对该细胞经N-甲基-N'-硝基-亚硝基胍(MNNG)或紫外线(UV)处理后DNA修复合成的影响。结果:0.1-10 μmol/L的CdCl2单独作用,细胞DNA修复合成前体物3H-TdR的掺入量与镉浓度量呈高度正相关的剂量-效应关系,其中10μmol／L剂量组与对照组相比差异有显著性;CdCl2在对人全血细胞UDS无明显诱导的剂量水平下即可使MNNG作用后DNA的修复合成受抑;与之相反,1μmol／L CdCl2与UV共同作用对人全血细胞UDS的诱导存在明显的协同作用。结论:较高浓度的镉对DNA具有损伤作用;而在较低浓度下,镉干扰DNA修复过程的作用较明显。上述直接和间接的遗传毒作用可能是镉致癌的机制之一。
文摘Background: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun-exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER-defective form of XP of seven complementation groups, designated XP-A to XP-G. These complementation groups correspond to different proteins involved in the NER process. XP-A classically includes some of the most severely affected patients. Objectives: We describe a 61-year-old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene. Methods: Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing. Results: Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP-A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A→ G at the eighth nucleotide of
