RESUMO

Free radicals produced during carbon tetrachloride biotransformation and the promoted lipid peroxidation process of liver microsomal lipids are able to attack the DNA bases guanine, cytosine and thymine to give at least three altered bases. They were identified as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua); 5-hydroxycytosine (5OHCyt) and 5-hydroxymethyluracil (5OHMeU). No adenine adducts were detected. If these altered bases were formed during carbon tetrachloride poisoning and were not adequately repaired before cell replication, serious permanent consequences for liver cell DNA could be expected and this might be somehow involved in the liver carcinogenic effects of the haloalkane.

Assuntos

Tetracloreto de Carbono/análogos & derivados , Tetracloreto de Carbono/farmacocinética , Adutos de DNA/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Animais , Biotransformação , Tetracloreto de Carbono/toxicidade , Citosina/análogos & derivados , Citosina/metabolismo , Dano ao DNA , Guanina/metabolismo , Masculino , Pentoxil (Uracila)/análogos & derivados , Pentoxil (Uracila)/metabolismo , Pirimidinas/metabolismo , Ratos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Timina/metabolismo

Assuntos

Dano ao DNA , Desoxiguanosina/análogos & derivados , Pentoxil (Uracila)/análogos & derivados , 8-Hidroxi-2'-Desoxiguanosina , Animais , Bovinos , Desoxiguanosina/metabolismo , Ácido Edético/farmacologia , Radicais Livres , Peróxido de Hidrogênio/toxicidade , Técnicas In Vitro , Ferro/farmacologia , Manitol/farmacologia , Oxigênio/metabolismo , Pentoxil (Uracila)/metabolismo