- Polynucleotide compounds for hybridizing to target polynucleotides
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Described is a polynucleotide compound comprising a polynucleotide which comprises at least one entity which upon hybridization to a complementary polynucleotide is capable of generating a detectable change in property in said hybrid, said entity being covalently or non-covalently attached by means of a linker arm to the base moiety, sugar moiety or phosphate moiety of a nucleotide in said polynucleotide, which polynucleotide compound may be used for detecting the presence of a target polynucleotide or for preventing the transcription or translation of a target polynucleotide.
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- ortho-Substituent effects on the in vitro and in vivo genotoxicity of benzidine derivatives
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Benzidine and its 3,3'-diamino, 3,3'-dimethyl, 3,3'-dimethoxy, 3,3'-difluoro, 3,3'-dichloro, 3,3'-dibromo, 3,3'-dicarbomethoxy and 3,3'-dinitro derivatives together with 2-nitrobenzidine and 3-nitrobenzidine were compared for their in vitro and in vivo genotoxicity. Relative mutagenicity was established with Salmonella strains TA98, TA98/1,8-DNP6 and TA100 with and without S9 activation. All the derivatives in the presence of S9 were more mutagenic than benzidine with 3,3'-dinitro- and 3-nitro-benzidine having the greatest mutagenicity. Mutagenicity in all 3 strains with S9 activation could be correlated to electron-withdrawing ability of substituent groups, as measured by the basicity of the amines. This correlation was explained on the basis that electron-withdrawing groups could favor the stability of the mutagenic intermediate N-hydroxylamine and also enhance the reactivityof the ultimate mutagenic species, the nitrenium ion. Mutagenicity was also correlated to the energy of the lowest unoccupied molecular orbitals (E(LUMO)). Hydrophibicity was found to have very limited effect on the relative mutagenicity of our benzidine derivatives. The in vivo endpoint was chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of benzidine and its derivatives. In contrast to the in vitro results, while all the amines were genotoxic in vivo, only the 3-nitro derivative had a significant increase in toxicity over benzidine.
- You,Brezzell,Das,Espadas-Torre,Hooberman,Sinsheimer
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