RESUMO
Double-stranded DNA is a one of the most important intracellular anticancer agent targets. Disturbance of DNA functions as well as DNA structure lead to disorder of such processes as transcription and/or translation thus inducing tumor cells death. Complex formation between novel dimeric bisbenzimidazole DB(7) and poly(dA-dT) duplex in comparison with known monomeric bisbenzimidazole MB(Ac) was investigated in this study. DB(7)-poly(dA-dT) binding constant was determined by fluorescence spectroscopy using Scatchard plot and it values 1.18 x 10(8) M(-1) that is two orders of magnitude larger than MB(Ac) one (2.06 x 10(6) M(-1)). Thus, from findings mentioned above it could be concluded that the presence of two bisbenzimidazole moieties in the ligand structure significantly increases its affinity to the polynucleotide which motivates the synthesis of new potential anticancer drugs based on dimeric bisbenzimidazoles.
Assuntos
Antineoplásicos/química , Bisbenzimidazol/análogos & derivados , Bisbenzimidazol/química , DNA/química , Corantes Fluorescentes/química , Oligodesoxirribonucleotídeos/química , Antineoplásicos/farmacologia , Bisbenzimidazol/farmacologia , Morte Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
The review considers the molecular biological organization of genome region pX of the human T-cell leukemia virus type I (HTLV-I) along with the structure and functions of regulatory proteins Tax, Rex, and poorly studied Rof and Tof. Tax functions are described, including transcriptional trans-activation, trans-repression, and effects on apoptosis and the cell cycle. The roles of Tax and Rex in controlling gene expression and replication of HTLV-I are discussed.
Assuntos
Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Linfoma de Células T/virologia , Proteínas Oncogênicas de Retroviridae/fisiologia , Fatores de Transcrição , Elementos Facilitadores Genéticos , Regulação Viral da Expressão Gênica , Produtos do Gene rex/fisiologia , Produtos do Gene tax/fisiologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas dos Retroviridae , Sequências Repetidas Terminais , Proteína Supressora de Tumor p53/genética , Proteínas Virais Reguladoras e Acessórias , Replicação Viral/fisiologiaRESUMO
Seroepidemiological and molecular-biological screening of 1510 donor blood samples, collected from the residents of the town of Ashgabat (Turkmenistan), for lymphotropic virus of human T-cellular leukemia (HTLV) virus revealed one donor with a high level of immune response to a wide spectrum of viral proteins. Three donors were serologically assessed as dubious, for their sera contained antibodies to gag gene protein but no antibodies to env gene protein. Screening of family members of the donor infected with HTLV-1 revealed four more highly reactive carriers of HTLV-1 virus. The presence of proviral sequences of HTLV-1 in the lymphocyte DNA of infected donor and her relatives was confirmed by polymerase chain reaction and subsequent Southern-blot hybridization of specific amplification products. Proviral sequences of gag, pol, and LTR genes were detected in all the cases. Short-term culturing of peripheral blood lymphocytes of all seropositive subjects was associated with expression of HTLV-1 structural proteins. Analysis of the possible routes of transmission of HTLV-1 isolated in Turkmenistan permits us to hypothesize an Iranian origin of the isolated virus strain.