Radioprotective effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothioronicadenosin-5-triphosphate (adeturon) in gamma-irradiated Escherichia coli cells.
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.
Fuentes
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Centro de Estudios Aplicados al desarrollo Nuclear (CEADEN), Calle 30 No. 502 e/ 5ta y 7ma, P.O.Box 6122, Miramar, Playa, Havana, Cuba.
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D010582:Bacteriophage lambda / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004050:Ditiocarb / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D029968:Escherichia coli Proteins; D005720:Gamma Rays / Q000009:adverse effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013014:SOS Response, Genetics / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D000338:beta-Aminoethyl Isothiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D011837:Radiation-Protective Agents; C053139:sulA protein, E coli; D000338:beta-Aminoethyl Isothiourea; C012704:Adeturon; D000255:Adenosine Triphosphate; D004050:Ditiocarb