N-MYC AMPLIFICATION AND ITS RELATIONSHIP TO EXPERIMENTAL-THERAPY

N-myc amplification correlates with poor prognosis in neuroblastoma pa tients. Although the reason for this is unclear, it is possible that a mplified N-myc confers resistance to certain agents used in the therap y of the disease. The acquisition of resistance to cytotoxic drugs in human tumour cells is multifactorial. One mechanism involved in the de velopment of drug resistance is an increased efficiency of DNA repair. This could reduce the effectiveness of both cisplatin and etoposide ( VP-16). Previous studies on human neuroblastoma cells have shown a rel ationship between N-myc copy number and cisplatin sensitivity [1]. We now report the response to VP-16 treatment of five human neuroblastoma cell lines with a range of N-myc gene copy numbers. After exposure of cells to drug for 24 hours, survival curves were constructed from clo nogenic assay data and the iso-effective dose (the dose required to pr oduce 1 log cell kill) was derived. The relationship between N-nzye co py number or expression and response to VP-16 was assessed. A signific ant correlation was established between VP-16 resistance and copy numb er (r = 0.82; P < 0.05). However, no association was found between N-m yc expression and isoeffective dose of VP-16. These results indicate t hat N-myc amplification may be responsible for treatment failure in th ose patients receiving cisplatin or VP-16.