Oncogens

Eadier reports of a link between testicular cancer and DMF exposure have not been corroborated ia a study of 4000 Du Pont employees (34). Very recendy, inhalation studies ia mice and rats have shown no oncogenic effect from DMF (35). The International Agency for Research on Cancer (lARC) has concluded that evidence associating DMF with cancer ia animals is "iaadequate," but has classified DMF as "possibly carciaogenic to humans" (Group 2B) (36). 

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

J. M. Smith and co-workers, "Methyl Methacrylate Subchronic, Chronic and Oncogenic Inhalation Safety Evaluation Studies," Mbstracts of the Eighteenth Mnnual Meeting of the Society of Toxicology, New Orleans, La., 1979. 

The relationship between the two receptors for NGF is complex and not yet completely understood. It has been suggested that the functional form of the NGF receptor is a heterodimer of p75 and pl40 proteins. BDNF and NT-3 bind to p75, but the functional receptors for these neurotrophins are the proto-oncogene products of and trkQ. 

The streptovaricins inhibit the reverse transcriptase of some RNA oncogenic vimses that may be involved in the process of viral transformation (see Antiviral agents). The atropisostreptovaricins again have similar activities to the corresponding natural isomers. The streptovals and streptovarone exhibit gready improved activity against reverse transcriptase relative to the streptovaricins (85), but their in vitro activities were low (86). The damavaricins also inhibit reverse transcriptase (4) as well as tumor cell growth (87). 

Biotechnology. Particular attention must be paid to the detection of DNA in all finished biotechnology products because of the possibiUty that such DNA could be incorporated into the human genome and thus become a potential oncogene. The absence of DNA at the picogram-per-dose level should be demonstrated in order to assure the safety of biotechnology products (157). 

Retroviridae Types B and C Oncovirus numerous leukemias, including friend. oncogenic of lower animals... 

Gross Moloney, Rauscher rous sarcoma, HIV oncogenic of fowl, aids... 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

Jumak, F. Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins. Science 230 32-36, 1985. 

Pai, E.F., et al. Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341 209-214,... 

Scheffzek, K., et al. The Ras-RasGAP complex structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277 333-338, 1997. 

Some occupational hygiene aspects of man-made mineral fibres and new technology fibres Safe handling requirements dunng explosive, propellant and pyrotechnic manufacture Simplified calculations of blast induced injuries and damage Laboratory work with chemical carcinogens and oncogenes Rosin (colophony) a review... 

TABLE 5.22 Important Oncogenes and Tumor Suppressor Genes in Human Cancers... 

Woodget, J. R., 1991. A common denominator linking glycogen metabolism, nuclear oncogenes, and development. Trends in Biochemical Sciences 16 177-181. 

Thiophene, 2,2-bithiophene, and 2,2, 5, 2"-terthiophene derivatives from Chinese medicinal plants as oncogene signal transduction inhibitors (proteinki-nase C inhibitors) 99PAC1101. 

Ravichandran KS (2001) Signaling via She family adapter proteins. Oncogene 20 6322-6330... 

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