Mutagen modulation

King-Batoon, A, JM Leszczynska, and CB Klein. 2008. Modulation of gene methylation by genistein or lycopene in breast cancer cells. Environ Mol Mutagen 46 36 -5. 

Benigni R, Bossa C, Jeliazkova N, Netzeva T, Worth A. The Benigni/Bossa rulebase for mutagenicity and carcinogenicity - a module of Toxtree. European Commission Report EUR... 

Nian H, Delage B, Ho E, Dashwood RH. (2009) Modulation of histone deacetylase activity by dietary isothio-cyanates and allyl sulfides Studies with sulforaphane and garlic organosulfur compounds. Environ Mol Mutagen 50 213-221. 

Hirayama T (1979) Naturally Occurring Carcinogens - Mutagens and Modulators of Carcinogenesis. In Miller EC, Miller JA, Hirono I, Sugimura T, Takayama S (eds) Japan Sci Soc Press-University Park Press Tokyo-Baltimore, p 359... 

Iqbal M, Okazaki Y, Okada S. 2003. In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H202)-induced peroxidation of microsomal membrane lipids and DNA damage. Teratog Carcinog Mutagen Suppl 1 151-160. 

Ishikawa, T. Takayama, S. Kitagawa, T. Kawachi, T. Kinebuchi, M. Matsukura, N. Uchida, E. Sugimura, T. "Naturally Occurring Carcinogens-Mutagens and Modulators of Carcinogenesis" Japan Sci. Soc. Press Tokyo/Baltimore, 1979 p. 159-167. 

Modulation of Mutagenesis by 3-carotene and 13-cis-Retinoic Acid. The provitamin 3-carotene, and a synthetic derivative of vitamin A, 13-cis-retinoic acid, were examined with respect to their capacity to modulate 2-fluorenamine-induced mutagenicity in Salmonella. These studies were carried out since dietary and serum levels of 3-carotene vary widely among humans. Also, there is considerable interest in the anti-tumor activity of 13-cis-retinoic acid and other synthetic retinoids. 

In no instance did the synthetic retinoid possess as great an inhibitory capacity as do retinol or retinyl acetate. In addition, the provitamin g-carotene had no effect on mutagenicity of 2-fluorenamine in Salmonella regardless of the carcinogen activation system (Tables III and IV). Thus, 3-carotene would apparently require enzymatic cleavage to vitamin A in order to have an effect in this ijri vitro bioassay and exerts no role by itself in modulating the metabolism of chemical carcinogens in the model system. 

Modulation of Mutagenicity by the Intestinal Carcinogen 3,21-Dimethyl-4-Aminobiphenyl. We wished to examine the effect of retinol, 3-carotene and 13-cis-retinoic acid on yet another aromatic amine,... 

The modulation of mutagenicity of aromatic amines in Salmonella is not a result of (a) PCB treatment of rats, or the presence of residual PCB s in liver preparations, (b) vagaries of the Salmonella plate test, or (c) the effect of retinoids upon bacterial viability. 

Similar effects were observed with the synthetic retinoid 13-cis-retinoic acid, while 3-carotene was without effect in modulating the mutagenicity of aromatic amines in Salmonella. 

In what follows, no explicit attention is given to the specific type of assays or tester strains used to determine the mutagenic activity in nitro-aromatic compounds. This particular choice is made consciously, as the emphasis of this work is on the structural and electronic factors that modulate the mutagenic activity of the nitro-aromatic compounds in general. The interested readers are recommended to refer to the original works for more detailed discussions. 

The most important conclusion to be made from these studies is the great importance of hydrophobicity in the modulation of the potential for mutagenicity and carcinogenicity. Hansch and coworkers have showed that compounds that require S9 activation to become mutagenic in bacteria all have log Kow terms with coefficients near 1.0 (Debnath et al., 1994). Other QSARs show that where a direct chemical reaction with DNA appears to occur, without metabolic activation, no hydrophobic term enters into the equation (Hansch et al., 2001). In these cases, usually only the electronic (reactivity) properties are important. Notable examples of QSARs based on electronic terms and without a hydrophobic term relate to the mutagenicity to Salmonella of aniloacridines, di-platinum analogs, lactones, and epoxides. All of these examples are for chemicals that do not require activation (Hansch et al., 2001). 

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