Induced and inherent resistance to alkylating agents in human small-cell bronchial carcinoma xenografts

Abstract

Inherent and induced resistance was investigated in human small-cell lung cancer xenografts. Specimens from three patients were established in immune suppressed mice; the sensitivity of the xenografts to cyclophosphamide, MeCCNU and melphalan was determined using the growth delay end-point. Clinical chemosensitivity data were available in two cases and inherent differences in sensitivity were noted both in the xenografts and clinically. Radioactively labelled melphalan uptake studies were performed with these two xenografts. A number of different strategies to induce resistance were explored. Only one method proved to be successful and in only one of the xenografts; this was with cyclophosphamide. The induced resistant line was characterised in terms of the time course of its production, the degree of induced resistance, the growth rate, the cross-resistance pattern and stability of the phenotype; the possibility of altered antigenicity was also examined.