Inherent sensitivity and induced resistance to chemotherapeutic drugs and irradiation in human cancer cell lines: relationship to mutation frequencies.
Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug-resistant disease following chemotherapy. Cell lines derived from testis tumors retain hypersensitivity to both drugs and radiation in vitro, thus providing a model system with which to investigate the genetic basis of hypersensitivity to these agents. This study compared the spontaneous and both ethyl methanesulfonate- and cisplatin-induced frequencies of mutation of 6-thioguanine resistance in 3 human bladder and 3 testis tumor cell lines and a bladder and a testis cell line with cisplatin resistance induced in vitro. The two tumor types showed similar frequencies of both spontaneous and induced mutation frequencies at this locus. Therefore, we failed to provide evidence for the hypothesis that the curability of testis tumors is associated with a low frequency of mutation to drug resistance.
Parris
C N
CN
University College London, Department of Pathology, St. Pauls Hospital, London, England.
Walker
M C
MC
Masters
J R
JR
Arlett
C F
CF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D009154:Mutation; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics*; D013866:Thioguanine / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics*
D000970:Antineoplastic Agents; D004247:DNA; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D002945:Cisplatin