thioguanine-anhydrous and Urinary-Bladder-Neoplasms

The mutagenic potentials of the human bladder carcinogen 4-amino-biphenyl (ABP) and three of its proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) were tested on a prime human target cell type for carcinogenesis, human uroepithelial cells (HUC). SV-HUC (PC), a near diploid, clonally derived, nontumorigenic SV40-immortalized human uroepithelial cell line that is transformable to tumorigenicity after exposure to ABP and its metabolites, was used for quantitative mutation assays. The end point used was the induction of mutations in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus, selected using 6-thioguanine resistance (TGr). A single, 24-h exposure of SV-HUC to ABP, N-OH-ABP, N-OH-AABP, or N-OAc-AABP caused a statistically significant, dose-dependent increase in mutation frequency resulting in a 2-30-fold increase in the number of TGr mutants in carcinogen-exposed groups compared to untreated controls. These chemicals were similarly mutagenic towards MC-T11, an SV-HUC-derived low grade tumor cell line that was also shown to be responsive to transformation (in a separate study) by ABP, N-OH-ABP, or N-OH-AABP as judged by the generation of higher grade tumors. In contrast, the mutagenic potencies of ABP and N-OH-ABP were lower when tested on a subclone of SV-HUC (BC) that is refractory to transformation by these chemicals. Thus, these data support a model of transformation in which ABP as well as its metabolites contribute to tumorigenic transformation and neoplastic progression of HUC by inducing mutations in susceptible target cell genes.

Topics: Aminobiphenyl Compounds; Cell Line, Transformed; Dimethyl Sulfoxide; Drug Resistance; Humans; Hypoxanthine Phosphoribosyltransferase; Methylnitronitrosoguanidine; Mutation; Simian virus 40; Thioguanine; Urinary Bladder Neoplasms

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.

Topics: Antineoplastic Agents; Cisplatin; DNA; Dose-Response Relationship, Drug; Drug Resistance; Ethyl Methanesulfonate; Humans; Hypoxanthine Phosphoribosyltransferase; In Vitro Techniques; Male; Mutation; Testicular Neoplasms; Thioguanine; Urinary Bladder Neoplasms

From June 1975 through December 1983, 48,604 individuals consisting of 34,535 males and 14,069 females underwent health examinations at the Automated Multiphasic Health Testing and Services (AMHTS) Center in Tokai University Hospital. There were five patients with renal cell carcinoma and three with bladder cancer. We reviewed the clinical courses of these patients and discussed the early detection of urological cancers in AMHTS. Patients with renal cell carcinoma were brought to the urology department with various findings in AMHTS. A 44-year-old male was referred to us for the investigation of multiple metastatic shadows in the chest X-P and left renal tumor was diagnosed by intravenous pyelography (IVP) and computed tomography (CT). Renal tumor of a 57-year-old male was diagnosed by the investigations of abnormal renal calcifications found in AMHTS. A 39-year-old female had undergone health check-ups several times but was not found to have a renal tumor. The diagnosis of left renal tumor was made by the abdominal CT carried out after the operation on cerebellar hemangioblastoma. The fourth patient was a 60-year-old female with microscopic hematuria found in AMHTS and the diagnosis was confirmed by calyceal deformity shown in IVP. The last patient was a 64-year-old male and was accidentally demonstrated to have a right renal mass by ultrasonography when he was reexamined for the hepatic abnormality found in AMHTS. He showed microscopic hematuria in the AMHTS urinalysis. The diagnosis was confirmed by IVP, CT and renal angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Cytarabine; Female; Hospitals, University; Humans; Japan; Kidney Neoplasms; Male; Middle Aged; Multiphasic Screening; Thioguanine; Ultrasonography; Urinary Bladder Neoplasms