Cell mutation

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

Mutagen — A substance that causes mutations. A mutation is a change in the genetic material in a body cell. Mutations can lead to birth defects, miscarriages, or cancer. 

Romert, L. and Jenssen, D. (1983). Rabbit alveolar macrophage-mediated mutagenesis of polycyclic aromatic hydrocarbons in V79 Chinese hamster cells. Mutat. Res. Ill, 245-252. 

Four major tissue layers, from the lumen outward, form the large intestine the mucosa, submucosa, muscularis externa, and serosa (Fig. 88-2). Complete replacement of surface epithelial cells occurs approximately weekly, with the total number of epithelial cells remaining constant in normal colonic tissue. As patients age, abnormal cells accumulate on the surface epithelium and protrude into the stream of fecal matter their contact with fecal mutagens can lead to further cell mutations and eventual adenoma formation.4... 

Figure 6. The c-mos negative regulatory element (NRE). Nucleotide positions of the NRE are shown relative to the spermatocyte transcription start site, taken as 280 base pairs upstream of the c-mos ATG (see Fig. 4). The endpoints of the NRE are defined by deletions that allow c-mos expression in NIH 3T3 and other somatic cells. Mutations of the sequences designated by boxes 1,2, and 3 also allow c-mos transcription in NIH 3T3 cells, indicating that these sequences represent functional elements within the NRE. Boxes 1 and 2 are similar to sequences upstream of the protamine (Prot) promoter that inhibit in vitro transcription in HeLa cell extracts. A sequence just upstream of box 2 is also similar to a putative repressor-binding site in the regulatory region of Pgk2.

Hartwig A. Schlepegrell R. Beyersmann D. 1990. Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells. Mutat Res 241 75-82. 

A natural progression from using CA to model bacterial growth is to model tumor growth and the development of abnormal cells. There has been considerable work on this topic. Features such as cell mutation, adhesion, layered growth, and chemotaxis can readily be incorporated into a CA model.5 Deutsch and Dormann s book provides a useful introduction to this area.6... 

The letter N indicates that any nucleotide at that position satisfies the specificity of Mstll. The normal sequence of the DNA of the 13-chain of hemoglobin A near the site of the sickle cell mutation is . ..C-C T-G-A-G-G. 

Rogers, A.M., and K.C.Back. 1981. Comparative mutagenicity of hydrazine and 3 methylated derivatives in L5178Y mouse lymphoma cells. Mutat. Res. 89 321-328. 

Ehrlich, E. 1990. The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on cell growth and the induction of DNA damage in Chinese hamster ovary cells. Mutat. Res. 244 299-302. 

Nagasawa, H., J.B. Little, W.C. Inkret, S. Carpenter, K. Thompson, M.R. Raju, D.J. Chen, and G.F. Stmiste. 1990. Cytogenetic effects of extremely low doses of plutonium-238 alpha particle irradiation in CHO K-l cells. Mutat. Res. 244 233-238. 

Unless otherwise stated, I use the terms "genetic" and "inherited" interchangeably to refer to the alleles that a person receives from his or her parents, and which could be transmitted to his or her children. I do not mean acquired somatic cell mutations or mutations in infectious agents. 

Bootman, J., G.Hodson-Walker, and J.M.Lloyd. 1988b. CFC141b Investigation of mutagenic activity at the HGPRT locus in a Chinese hamster V79 cell mutation system. 88/ PSV005/257, Life Science Research Laboratory, EYE, Suffolk, England (Cited in ECETOC 1994). 

Cifone, M.A., Myhr, B., Eiche, A. and Bolisfodi, G. (1987). Effect of pH shifts on the mutant frequency at the thymidine kinase locus in mouse lymphoma L5178Y TK+/— cells. Mutation Res. 189 39-46. 

Clive, D., Flamm, W.G. and Patterson, J.B. (1972). A mutational assay system using the thymidine kinase locus in mouse lymphoma cells. Mutation Res. 16 77-87. 

Ehling, U.H., Chu, E.H.Y., DeCarli, L., Evans, H.J., Hayashi, M., Lambert, B., Neubert, D., Thilly, W.G. and Vainio, H. (1986). Report 8. Assays for germ-cell mutations in mammals. In Long-term and Short-term Assays for Carcinogens. (Montesano, R., Bartsch, H., Vainio, H., Wilboum, J. and Yamasaki, H., Eds.). A Critical Appraisal. IARC Scientific Publications, No. 83, Lyon, pp. 245-265. 

Thust, R., Mendel, J., Schwarz, H. and Warzoki, R. (1980). Nitrosated urea pesticide metabolites and other nitrosamides. Activity in clastogenicity and SCE assays, and aberration kinetics in Chinese hamster V79-E cells. Mutation Res. 79 239-248. 

Paschin YV, Bahitova LM. 1982. Mutagenicity of benzo[a]pyrene and the antioxidant phenol at the HGPRT locus of V79 Chinese hamster cells. Mutat Res 104 389-393. 

Tsutsui T, Hayashi N, Maizumi H, et al. 1997. Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells. Mutat Res 373 113-123. 

Clive, D. and Spector, J.F.S., Laboratory procedure for assessing specific locus mutations at the TK locus in cultured L5178Y mouse lymphoma cells, Mutat. Res., 31, 17, 1975. 

Wancer is one of the leading causes of death in Canada. It is a disease in which cells mutate and grow at uncontrolled rates, disrupting the body s normal functions. TAXOL , shown at the bottom of the page, is an organic compound that is found in the bark of the Pacific yew tree. After many tests and reviews, TAXOL was approved for use in treating ovarian cancer. 

Skov, K.A., 1999, Radioresponsiveness at low doses hyper-radiosensitivity and increased radioresistance in mammalian cells, Mutat.Res. 430 241-253. 

Natural selection increases or decreases allele frequencies, depending on their survival value (e.g., heterozygote advantage for the sickle cell mutation)... 

Answer . The frequency of sickle cell disease is elevated in many African populations because heterozygous carriers of the sickle cell mutation are resistant to malarial infection but do not develop sickle cell disease, which is autosomal recessive. Thus, there is a selective advantage for the mutation in heterozygous carriers, elevating its frequency in the population. 

Type 1 diabetes affects approximately 1 in 200 Americans, with a sibling recurrence risk of about 6%. It is an example of an autoimmune disease (see Immunology Lecture Notes), in which self-reactive T cells infiltrate the pancreas to destroy insulin-produdng islet cells. Mutations in the class II major histocompatibility locus (MHC) region are estimated to contribute about one third of the risk of developing type 1 diabetes. Mutations in or near the insulin gene itself are responsible for another 10-15% of the risk. 

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