Analysis of DNA repair synthesis in peripheral blood lymphocytes from patients with well-controlled and uncontrolled asthma

10641 Breast cancer is the most common malignancy among women and its rate of mortality is still high. The increase knowledge of breast cancer biology is heaving great impact on determining the clinical prognosis and response to treatment. Impaired DNA repair may elevate the risk of malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. The present study was designed to evaluate the relationship between DNA damage and expression of some critical genes including TP53, c-ERBB2, ER (Estrogen Receptor) and PR (Progesterone Receptor) in breast cancer. Blood samples were obtained from female patients with diagnosed breast cancer before chemotherapy as well as from healthy individuals, and were processed in 24 hours. To evaluate the role of DNA repair in breast cancer we determined the level of DNA damage and the capacity to remove DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes. For this purpose the alkaline version of the comet assay, which provides a sensitive tool to investigate DNA damage and repair, was applied. The level of basal DNA damage was higher in breast cancer patients compared to the control group. Considerable inter-individual variations of DNA damage and repair in breast cancer patients were observed both before and after the treatment. The correlation between DNA damage in peripheral blood and expression of p53, c-erbB-2, PR and ER was analyzed. This preliminary study indicates that the DNA damage accumulation, observed in peripheral blood lymphocytes of breast cancer patients in early stages, could be attributed to impaired DNA repair. Our results suggest that DNA damage, as evaluated by the comet assay, seems to be useful molecular biomarker for monitoring ongoing exposures to DNA damaging agents. Such a research on the mutagen sensitivity and efficacy of DNA repair could impact on the development of new diagnostic and screening strategies. Work Supported by FAPERGS and GENOTOX (UFRGS). No significant financial relationships to disclose.

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Chemical carcinogen induction of DNA-repair synthesis in human peripheral blood monocytes

Mutation Research/Environmental Mutagenesis and Related Subjects ◽

10.1016/0165-1161(80)90194-6 ◽

1980 ◽

Vol 74 (5) ◽

pp. 357-377 ◽

Cited By ~ 17

Author(s):

Robert S. Lake ◽

Melvin L. Kropko ◽

Sandra McLachlan ◽

Mary R. Pezzutti ◽

Robert H. Shoemaker ◽

...

Keyword(s):

Dna Repair ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Chemical Carcinogen ◽

Blood Monocytes ◽

Repair Synthesis ◽

Peripheral Blood Monocytes ◽

Dna Repair Synthesis

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Study of DNA Repair in the Peripheral Blood Lymphocytes of Patients with Rheumatic Diseases Under Going Treatment

Advances in Experimental Medicine and Biology - Purine and Pyrimidine Metabolism in Man VII ◽

10.1007/978-1-4899-2638-8_87 ◽

1991 ◽

pp. 383-385

Author(s):

A. Lukšienė ◽

R. Filipavičiūtė

Keyword(s):

Dna Repair ◽

Rheumatic Diseases ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Blood Lymphocytes

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SENSITIVITY TO 4-HYDROXYESTRADIOL AND DNA REPAIR EFFICIENCY IN PERIPHERAL BLOOD LYMPHOCYTES OF ENDOMETRIAL CANCER PATIENTS

Experimental Oncology ◽

10.31768/2312-8852.2018.40(1):68-72 ◽

2018 ◽

Vol 40 (1) ◽

pp. 68-72 ◽

Cited By ~ 1

Author(s):

L G Buchynska ◽

O V Brieieva

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Endometrial Cancer ◽

Family History ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Blood Lymphocytes ◽

Repair Efficiency ◽

History Of ◽

History Of Cancer

Background: The development of hormone-dependent cancers, including endometrial carcinomas, in great part may be mediated by the genotoxic effects of estrogen metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most prominent DNA-damaging properties. It is assumed that the individual sensitivity to the 4OHE2 may determine the predisposition to endometrial cancer (EС). Aim: To analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to the 4OHE2 and to evaluate the repair efficiency of 4OHE2-induced DNA damage. Materials and Methods: The study was performed on the PBLs of 53 EC patients and 20 healthy women. The level of DNA damage was measured using the comet assay and was expressed as % tail DNA. The DNA repair efficiency (%) was evaluated by determining the ratio between the amount of repaired DNA damage and the level of 4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2. Results: In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 ± 2.2% tail DNA) and lower DNA repair efficiency (34.0 ± 4.5%) was observed compared to PBLs of healthy women (22.3 ± 2.3% tail DNA and 48.8 ± 4.5%, respectively). PBLs of EC patients with deep tumor invasion of myometrium were characterized by more prominent decrease of DNA repair than those with less invasive tumor (< ½ of myometrium) (20.9 ± 7.8 and 43.7 ± 6.7%, respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs of EC patients with a family history of cancer compared to this parameter in patients with sporadic tumors (20.9±7.8 and 47.1 ± 5.5%, respectively). Conclusion: The PBLs of EC patients are characterized by increased sensitivity to the genotoxic effect of 4OHE2 and reduced repair efficiency regarding 4OHE2-induced DNA damage. A lower level of DNA repair is observed in EC patients with deep tumor myometrial invasion and a family history of cancer.

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