Screening of new anticancer agents in vitro using panels of human cell lines derived from non-seminomatous germ cell tumours and transitional cell carcinomas of the bladder.
Metastatic testis tumours are cured in over 80% of patients using combination chemotherapy, and this hypersensitivity is retained by the cells in vitro. To determine whether differential toxicity to testis tumour cells is useful in the screening of novel anticancer agents, we compared the toxicities of 12 compounds against panels of human bladder and testis tumour cell lines using a clonogenic assay. The compounds had screened negative against P388 in vivo, and had been retested using the human tumour colony forming assay (HTCFA) and in selected cases against human tumour xenografts. NSC 339004, chloroquinoxaline sulphonamide, was 7-fold more toxic to testis tumour than bladder cancer cells, comparing the mean of the concentrations reducing colony-forming ability by 70%. This was the only one of the compounds selected by the HTCFA shown to have clinical activity. Compound R was selectively toxic to the bladder cancer cells, and might be of value as an intravesical agent. These data indicate that panels of testis and bladder cancer cell lines might be a useful addition to the disease-oriented screening programme.
Masters
J R
JR
University College London, Institute of Urology and Nephrology, U.K.
Jenkins
W E
WE
Shoemaker
R H
RH
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D013736:Testicular Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents