Genetic basis of drug sensitivity in human testis tumour cells.
Testicular germ cell tumours (TGCT) are cured in over 80% of patients by using combination chemotherapy. However, the mechanism regulating this sensitivity has not been defined. Because cells derived from patients with DNA repair syndromes are similar to TCGT in their sensitivity to certain DNA-damaging agents and some of the genes involved have been cloned by functional complementation, the purpose of our study was to determine whether drug sensitivity in TGCT also has a genetic basis. Three testis tumour cell lines (cisplatin-sensitive) and 3 bladder cancer cell lines (cisplatin-resistant) were fused with a cisplatin-sensitive cell line (D98orC1). The authenticity of the hybrids was confirmed by karyotyping and PCR analysis of locus-specific sites, and sensitivities to cisplatin were measured by colony forming assays. The hybrids between sensitive cell lines were more resistant to cisplatin than the parental cells, indicating that functional complementation had occurred. The hybrids between the cisplatin-resistant and sensitive cells were intermediate in their cisplatin sensitivity, indicating that resistance is incompletely dominant. We conclude that cisplatin sensitivity has a genetic basis in TGCT and that resistance to cisplatin can be conferred by somatic cell fusion. Our data indicate that gene(s) controlling sensitivity to chemotherapy in TGCT might be identified by expression cloning.
Wang
X
X
Institute of Urology and Nephrology, University College of London, United Kingdom.
Hafezparast
M
M
Masters
J R
JR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004351:Drug Resistance / Q000235:genetics; D018237:Germinoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin