Fuentes J L, Capetillo N, Ferrer M, Padrón E, Altanés S, Llagostera M
Centro de Estudios Aplicados al desarrollo Nuclear (CEADEN), Calle 30 No. 502 e/ 5ta y 7ma, P.O.Box 6122, Miramar, Playa, Havana, Cuba.
Mutat Res. 1998 Dec 3;422(2):339-45. doi: 10.1016/s0027-5107(98)00166-3.
The effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothiouronicadenosin-5-triphosphate (adeturon) in the induction of Escherichia coli SOS response promoted by gamma-irradiation was studied by measuring the induction of sulA gene and the induction of lambda prophage. Furthermore, as a way of measure the exonuclease activity in gamma-irradiated cells in the presence or absence of both compounds, the DNA degradation was determined. Adeturon did not affected DNA degradation, but inhibited the induction of the SOS functions studied. On the contrary, DDC inhibited DNA degradation as well as the induction of the sulA gene, but enhanced lambda induction in E. coli lysogenic strains. These results indicate that both compounds diminish the DNA damage produced by gamma-irradiation and also suggest that the mechanisms of radioprotection must be different. Thus, radioprotection mediated by DDC should involve free hydroxyl radical scavenging and a minor activity of exonuclease. The enhancement of phage induction in E. coli cells that DDC produces could be attributed to its quelant effect and this would not be not probably directly related to radioprotection. Adeturon, as thiols, may serve also as scavenging agent of free hydroxyl radicals, diminishing indirectly the DNA damage level. In addition, adeturon must interact with DNA in the same form that other aminothiol compounds do it. This interaction, mediated by amino groups of adeturon, may serve to concentrate these compounds near of the DNA damage site, increasing the potential for the thiol portion of the molecule to donate hydrogen, decreasing the damage level on DNA molecule. However, adeturon do not modify the exonuclease activity. Some topic about the possible clinical application of both compounds are discussed.
通过测量sulA基因的诱导和λ原噬菌体的诱导,研究了二乙基二硫代氨基甲酸钠(DDC)和S-2-氨基乙基异硫脲核苷-5-三磷酸(阿德图隆)在γ射线诱导大肠杆菌SOS反应中的作用。此外,作为测量在有或没有这两种化合物的情况下γ射线照射细胞中外切核酸酶活性的一种方法,测定了DNA降解情况。阿德图隆不影响DNA降解,但抑制了所研究的SOS功能的诱导。相反,DDC抑制DNA降解以及sulA基因的诱导,但增强了大肠杆菌溶原菌株中的λ诱导。这些结果表明这两种化合物都减少了γ射线照射产生的DNA损伤,也表明辐射防护机制一定不同。因此,DDC介导的辐射防护应涉及清除游离羟基自由基和轻微的外切核酸酶活性。DDC在大肠杆菌细胞中产生的噬菌体诱导增强可能归因于其螯合作用,这可能与辐射防护没有直接关系。阿德图隆作为硫醇,也可作为游离羟基自由基的清除剂,间接降低DNA损伤水平。此外,阿德图隆必须以与其他氨基硫醇化合物相同的方式与DNA相互作用。这种由阿德图隆的氨基介导的相互作用可能有助于将这些化合物集中在DNA损伤位点附近,增加分子中硫醇部分提供氢的潜力,降低DNA分子上的损伤水平。然而,阿德图隆不改变外切核酸酶活性。讨论了关于这两种化合物可能的临床应用的一些话题。