RESUMO
Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Quebras de DNA de Cadeia Simples , Escherichia coli/genética , Resposta SOS em Genética/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutação , Regiões Promotoras Genéticas , Transcrição Gênica , Raios Ultravioleta , Regulação para CimaRESUMO
In order to investigate aspects of the infection and morbidity of Chagas' disease in the municipality of JoÒo Costa, PiauÝ State, Brazil, we carried out a serological survey to detect anti-Trypanosoma cruzi antibodies in 2,080 individuals, by indirect immunofluorescence, indirect hemagglutination and ELISA. A total of 189 seropositive and 141 seronegative patients were evaluated by anamnesis, physical exam and electrocardiogram (EKG). The parasitaemia of 106 chagasic patients was evaluated by indirect xenodiagnosis and PCR (polymerase chain reaction). The total seropositivity was 9.8, with intervals of 0.5 in patients younger than 10 years old, and 39.4 among patients older than 59 years old, independently of the sex. The PCR and xenodiagnosis were positive, respectively in 74.5 and 15.1 of the seropositive patients (p < 0.05). The rate of abnormal EKG was 41.3 in chagasic and 15.6 in non-chagasic patients (p < 0.05). In spite of the high prevalence of infection in the investigated population, the low rate of seropositivity among children is indicative of a possible decrease of the active transmission mediated by triatomines. The high proportion of the chagasic component on the cardiopathy prevalence is indicative of the high morbidity of Chagas' disease in the studied region.
