Differential formation, repair and tolerance of Cisplatin-induced DNA damage in two human small cell lung carcinoma cell lines

Abstract

Chemotherapy unequivocally improves survival in small cell carcinoma (SCLC), even curing a small fraction of patients with limited disease, although drug refractory distant metastases are the most common cause of treatment failure [1]. The effectiveness of Cisplatin in treating SCLC is often limited by the development of drug resistance. Laboratory-based investigations of mechanisms associated with the expression of resistance to Cisplatin [2] have implicated various factors including: reduced drug accumulation; enhanced drug inactivation involving glutathione (GSH) or the metallothioneins (MT); differential DNA damage and repair; increased DNA damage tolerance. In this study our objective was to characterise the parameters associated with inherent differential Cisplatin sensitivities identified in 2 human SCLC cell lines, both established from patients not previously treated with Cisplatin, so as to determine whether the mechanisms operating in the more resistant subline were similar to or different from those associated with Cisplatin resistance expressed by in vitro drug-selected sublines.