Squamous cell carcinoma especially of oral cavity is one of the most prevalent diseases in the world. Chromosomal rearrangements are known to play important role in the pathogenesis of many diseases including cancer. In case of Head and Neck Squamous Cell Carcinoma, chromosomal changes are detectable at all stages of tumor development providing excellent opportunity for chromosomal prognosis and therapy. The present work aimed to study the frequency and pattern of chromosomal aberrations in human peripheral blood lymphocyte culture of freshly diagnosed Head and Neck squamous cell carcinoma patients. Further In vitro anticancer drugs (5-Fluorouracil {5-FU } and Cisplatin) effects were studied for clastogenicity. Results indicated significant impact of chemotherapeutic agents on the frequency of different types of chromosomal rearrangements.
Key words: chromosomal aberrations, head and neck squamous cell carcinoma (HNSCC), invitro chemotherapy, peripheral blood lymphocyte culture (PBLC)Oral squamous cell carcinoma (OSCC) is a major cause of morbidity and mortality worldwide, accounting for more than 275,000 new cases and over 120,000 deaths every year [1]. It is already known that non-random chromosomal aberrations occur in all human cancer types including squamous cell carcinoma (SCC) of the head and neck (HNSCC) [2]. Further many reports suggested that chromosomal aberrations and accumulation of mutations in many genes encoding crucial proteins or oncoproteins that control cell growth and apoptosis may also induce neoplastic formation [3,4,5]. However in case of Head and Neck SCC, chromosomal aberrations are found to be a dominant genetic event in carcinogenesis and may play an important role in cancer progression [6].In the present study, chromosomal rearrangements were observed in freshly diagnosed HNSCC patients who had not undergone any chemotherapeutic and/or radiation treatment. Further, peripheral blood lymphocytes of patients were exposed to anticancer drugs namely 5-Fluorouracil {5-FU} and Cisplatin commonly used for oral cancer treatment.5-FU is considered to be purely an S phase active chemotherapeutic agent [7] and also causes DNA damage, specifically double strand (and single-strand) breaks, during synthetic phase of cell cycle due to the misincorporation of FdUTP into DNA [8,9]. On the other hand, Cisplatin is a potent anti-tumor agent being cytotoxic to tumor cells via DNA-protein and DNA-DNA interstrand and intrastrand crosslinks [10]. The drug may also induce programmed cell death or apoptosis [11].Therefore, it is important to improve the patient survival rate in HNSCC and it is essential to find more accurate prognostic markers, if any, such as chromosomal rearrangements with different end points.
Materials and MethodsLymphocyte Culture.Lymphocyte cultures were set by method of Hungerford [12] with slight modifications [13]. Heparinized whole blood (0.5 ml) was added to a mixture containing 5 ml of culture medium RPMI 1640 and 0.1 ml phytohemagglutinin (Lectin). Then the culture vials were ke...