Carcinogenesis Mutation

Moser GJ, Robinette CL, Smart RC. 1993. Characterization of skin tumor promotion by mirex structure-activity relationships, sexual dimorphism and presence of Ha-ras mutation. Carcinogenesis 14(6) 1155-1160. 

Branibilla G, Cavanna M, Pino A, et al. 1981. Quantitative correlation among DNA damaging potency of six N-nitroso compounds and their potency in inducing tumor growth and bacterial mutations. Carcinogenesis 2 425-429. 

Ashby, J., and D. Paton (1993). The Influence of Chemical Structure on the Extent and Sites of Carcinogenesis for 522 Rodent Carcinogens and 55 Different Human Carcinogen Estytosurts."Mutation Research 286, 3-74. 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

If enzymes responsible for DNA repair are unable to remove the DNA adduct, or if an error takes place in the repair, then the error in the genetic code remains when the cell divides. Thus, cellular proliferation is also required, in addition to a mutation, for there to be a permanent effect of a chemical compound. Accumulation of genetic errors, i.e., mutations, has been suspected to be an important factor in chemical carcinogenesis. ... 

Soini, Y., Welsh, J. A., Fshak, K. G., and Bennet, W. P. (1995). p53 mutations in primary hepatic angiosarcomas not associated with vinyl chloride exposure. Carcinogenesis 16, 2879-2881. 

Some authors use the term mutation as a synonym for genetic polymorphism. However, it is recommended to reserve the term mutation for genetic variations acquired within the life span of an organism such as those mutations acquired in tumor tissues during multi-step carcinogenesis. 

Little known about consequences of mutation other than carcinogenesis... 

Blum, C.A. et al., F romotion versus suppression of rat colon carcinogenesis by chlorophyllin and chlorophyll Modnlation of apoptosis, cell proliferation, and 3-catenin/Tcf signaling, Mutat. Res., 523, 217, 2003. 

Nassi-Calo, L., Mello-Filho, A.C. and Meneghini, R. (1989). 0-Phenanthroline protects mammalian cells from hydrogen peroxide-induced gene mutation and morphological transformation. Carcinogenesis 10, 1055-1057. 

FIGURE 20.2 The involvement of RARE on apo-lO -lycopenoic acid-transactivated RARp expression. Upper panel Diagram of the RARp reporter vector with wild type and mutated R AREs. Lower panel HeLa cells transfected with the RARp reporter vector and an internal control vector were treated with 5 pmol/I. of apo-lO -lycopenoic acid or 1 pmol/L of all-trans retinoic acid for 24h. Luciferase activities were measured by dual-luciferase reporter system. Values are means of SEM of three replicate assays., statistically significantly different, as compared with control in the same group, P < 0.05. (Adapted from Lian, F. et al., Carcinogenesis, 28, 1567, 2007. With permission.)... 

The base substitutions are primarily transversions at G C base pairs and the available evidence suggests that these mutations are induced by apurinic sites which are generated as secondary consequences of the initial alkylation event. The significance of these results in the context of carcinogenesis is briefly considered. 

Although aminoacyl-tRNA synthetases are necessary for protein synthesis in all tissues, their importance in chemical carcinogenesis is difficult to assess. Mutation induction by this pathway has been studied extensively (123), yet metabolic activation in a carcinogen-target tissue has not been demonstrated. The only exception is hepatic prolyl-tRNA synthetase activation of N-hydroxy-Trp-P-2 however, hepatic O-acetylation of this substrate also occurs to an appreciable extent (12). Further investigations involving the use of specific enzyme inhibitors would be helpful in addressing this problem. 

Lee, T.C., M. Oshimura, and J.C. Barrett. 1985. Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture. Carcinogenesis 6 1421-1426. 

Hein DW. Molecular genetics and function of NAT1 and NAT2 role in aromatic amine metabolism and carcinogenesis. Mutat Res 2002 506-507 65-77. 

Random somatic mutation is thought to he a major event in carcinogenesis which may result from exposure to radiation,... 

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