Mutations bladder cancer

Sidransky, D., Eschenbach, A. V., Tsai, Y. C., Jones, P., Summerhayes, I. etal.. Identification of p53 gene mutations in bladder cancers and urine samples. Science 252, 706-709 (1991). 

Proteases are involved also in the expression of mutations in bacteria, in tumor promotion in mice, and in the X-ray-induced neoplastic transformation in hamster and mouse cells (21,22). Protease inhibitors will block tumor promotion in mice (23) and plant protease inhibitors in the diet have been proposed to account for the low incidence of breast and bladder cancer in countries where diet is high in plant proteins. 

Ras, the first oncogene found to be associated with a human tumour, an urinary bladder cancer, had a point mutation, changing a valine to a glycine. Other point mutations in ras... 

DOT CLASSIFICATION 6.1 Label KEEP AWAY FROM FOOD SAFETY PROFILE Confirmed carcinogen with experimental tumorigenic data. Along with p-naphthylamine and benzidine, it has been incriminated as a cause of urinary bladder cancer. Poison by subcutaneous and intraperitoneal routes. Moderately toxic by ingestion. Mutation data reported. Combustible when exposed to heat or flame. Incompatible with nitrous acid. To fight fire, use dry chemical, CO2, mist, spray. When heated to decomposition it emits toxic fumes of NOx. See also 2-NAPHTHYLAMINE and AROMATIC AMINES. 

Kannio A, Ridanpaa M, Koskinen H, et al. 1996. A molecular and epidemiological study on bladder cancer P53 mutations, tobacco smoking, and occupational exposure to asbestos. Cancer Epidemiol Biomarkers Prev 5 33-39. 

The frequency of active ras oncogenes in human bladder cancer (F6) associated with schistosomiasis was examined. Of nine squamous cell carcinomas of the bladder, none scored as positive in the regular DNA transfection assay. The restriction fragment polymorphism assay at codon 12 of the H-ras gene confirmed the absence of an activating mutation at this site in all samples. Western blotting analyses of the ras p21 proteins suggested a point mutation with codon 61 in one sample only. Enhanced expression of the ras p21 protein was demonstrated in four samples. 

The carcinogenic process involved in endemic bilharzial bladder cancer is thus not associated with detectable point mutations with ras genes at a higher frequency than occurs in nonbilharzial bladder cancer. 

The tumor suppressor gene p53 orchestrates the transcriptional regulation of cell cycle control elements. p53 mutations represent the most common genetic alterations in human malignancies.2 ° A number of studies have revealed p53 mutations in 40% to 60% of invasive bladder cancers and their association with a worse prognosis.2 1295 altered protein product of... 

Fujimoto K, Yamada Y, Okajima E, et al. Frequent association of p53 gene mutation in invasive bladder cancer. Cancer Res. 1992 52 1393. 

Miyamoto H, Kubota Y, Shuin T, et al. Analyses of p53 gene mutations in primary human bladder cancer. Oncol Res. 1993 5 245. 

Miyamoto H, Kubota Y, Fujinami K, et al. Infrequent somatic mutations of the pl6 and pl5 genes in human bladder cancer pl6 mutations occur only in low-grade and superficial bladder cancers. Oncol Res. 1995 7 327. 

Fig. 4 Percentage of tumor mutations at p53 base pairs with purine on the nontranscribed strand. The strand bias of several types of mutations affecting purines is shown in several common human cancers. A strong strand bias is indicative of a possible perturbation of the transcription-repair complex at an adducted DNA base. CpG transitions show almost equal distribution on both strands. GC to TA transversions show a strong strand bias in most cancers. The strong bias of AT to GC transitions in lung and bladder cancer is a clue to the involvement of carcinogens in the genesis of these mutations.

Tobacco smoking, occupational exposure to certain chemical dyes, and inflammatory reactions to parasitic and other infections account for the majority of the bladder cancer cases in the world. The burden of DNA sequence alterations is expected to increase in cells exposed to mutagenic agents from these exposures, such as 4-aminobiphenyl and other aromatic amines derived from tobacco smoke and dye mixtures, or nitric oxide released during inflammatory responses. Forty to fifty percent of bladder tumors contain mutant p53 alleles, and in a number of cases two distinct, nonsilent point mutations have been found in the same tumor. 

Comparison of mutations in lung and bladder cancers of smokers reveals that the same complex mixture, tobacco smoke, can induce different types of mutations in different tissues. Differences in exposure routes, tissue-specific metabolic pathways, and distribution of exposure components and their metabolites are expected to account for dissimilarities. DNA adduct measurements in various tissues following exposure to tobacco smoke or smoke condensate indicate there are shifts in the predominant tobacco smoke-derived DNA damaging agents in various organs. 

Breast cancer is one of the types of cancer that frequently arises in Li-Frau-meni syndrome families (Kleihues et al., 1997). The mutations found in Li-Fraumeni patients with breast cancer could be representative of background mutations that arise spontaneously in breast cancer. Comparison with sporadic breast cancer shows that two types of mutations, G to T and G to C transversions, have not been found in breast cancer patients in Li-Fraumeni families and thus could be specific for somatic breast cancer. These transversions represent only 18% of all breast cancer mutations. However, they show a strong strand bias and occur at sites also mutated in lung cancers from smokers (G to T transversions, codons 157,248,249 and 273) or in bladder cancers from smokers and/or dye-exposed workers (G to C transversions, codons 158 and 280). 

Toxicology LD50 (oral, mouse) 17 g/kg mild acute toxicity by ing. may cause allergic reactions incl. urticaria, nausea, vomiting, diarrhea has been linked to bladder cancer in test animals not considered human carcinogen by recent findings experimental teratogen, reproductive effects mutation data reported TSCA listed... 

Yu MC, Ross RK (1998) Epidemiology of bladder cancer. In Petrovich Z, Baert L, Brady LW (eds) Carcinoma of the bladder. Innovations in management. Springer, Berlin, pp 1-13 Yu MC, Skipper PL, Tannenbaum SR, Chan KK, Ross RK (2002) Arylamine exposures and bladder cancer risk. Mutat Res/Fundam Mol Mech Mutagen 506-507 21-28. http //www.doi. org/10.1016/S0027-5107(02)00148-3... 

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