DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin- Introduction

A Special Author Introduction
Melanoma Research

ISSN: 0960-8931 • Frequency: 6/year • Subscribe Now

By Fernanda Shimabukuro and Gilka J. Gattás

Cutaneous melanoma is a malignant tumor originated from epidermal melanocytes, highly invasive and aggressive, with high mortality, and incidence that has been increasing over the years. The treatment for melanoma is surgery and patients with metastasis may receive chemotherapy with cisplatin, a platinum agent, which leads to DNA adducts that alters the replication process in cancer cells. It is suggested that the DNA repair systems have an important role in the etiology of melanoma (risk due to deficient repair) and treatment efficiency (removal of DNA adducts can decrease the treatment results). Resistance to chemotherapeutic drugs can be an obstacle to a successful treatment of cancer patients in part associated to individual response and differences in the DNA repair system. Thus, the prior identification of the response of melanoma patients to treatment with cisplatin may be an important biological marker in clinical oncology.
The Comet assay, also referred as the single cell gel electrophoresis (SCG or SCGE) assay, is a sensitive, rapid and relatively inexpensive technique for quantitatively assessment of DNA breakage and repair in cultured or uncultured single cells. The Comet assay is an informative test to investigate DNA damage and repair in a wide range of tumor cells in response to a variety of DNA-damaging agents, including chemotherapeutic drugs.

The aim of this study was to assess, in peripheral blood leukocytes from melanoma patients and controls, the DNA damage before and after the addition of cisplatin (10µM, 100µM and 250μM), in vitro, and estimate the capacity of DNA repair after drug removal (1h, 2.5h and 5h) using the Comet assay. Cytogenetic analysis was performed in 20 patients with melanoma at an early stage and 19 cancer-free individuals who also answered a questionnaire on habits and types of exposure to risk factors for melanoma.

The results of the present study indicate that patients and controls differently responded to cisplatin treatment but had similar behavior regarding the capacity of DNA repair. Other experiments are necessary to evaluate if this repair is indeed efficient and able to cause resistance in a chemotherapy treatment. The use of leukocytes to establish a correlation between the DNA cell damage and repair of cisplatin-induced crosslinks and chemotherapy outcome would have an important clinical implication in the choice of chemotherapeutic agents to each cancer patient, increasing the potential for antitumor activity while reducing unnecessary toxicity in those who are unlikely to benefit.

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