RESUMO
AIM: Human cytochrome P450 3A and glutathione S-transferase (GST) enzymes evolved to catalyze the metabolism of numerous common therapy drugs and endogenous molecules. Members of the CYP3A are the majority expressed in human liver and intestine. The genetic factors play an important role in the interindividual variability in CYP3A and GST activity. Detection of CYP3A4 and GST variant alleles and knowledge about their allelic frequency in specific ethnic groups are important to lead to individualized drug dosing and improved therapeutics. METHODS: We determined the allelic frequency of the CYP3A4*18 and GSTP1 in a group of 138 healthy Tunisian subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. It is based on a specific PCR product cut by restriction endonucleases. This method offers the advantage of cutting DNA by the appropriate restriction enzyme at the correct mutation site hence enhancing its reliability. Electrophoretic separation demonstrates the presence (or absence) of restriction sites. RESULTS: In the group of 138 unrelated individuals, the frequencies of the CYP3A4*18 and GSTP1 variant allele in this Tunisian population were 0.02 and 0.01, respectively. CONCLUSIONS: The present study describes polymorphisms of Cyp3A4 and GST among Tunisian subjects. We developed a simple assay for the detection of the CYP3A4*18 and GSTP1 polymorphisms and we compared our allelic frequencies to other populations. No significant difference was obtained. This study provides the first analysis of CYP3A4*18 and GSTP1 mutant allele frequencies in the Tunisian population.
Assuntos
População Negra/genética , Citocromo P-450 CYP3A/genética , Glutationa S-Transferase pi/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Sistema Enzimático do Citocromo P-450/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Tunísia , Adulto JovemRESUMO
Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein regulating haematopoiesis, has recently been shown to exert an important cyto-protective effects in many tissues. The purpose of this study was to explore whether rhEPO protects against Cisp-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: control group, rhEPO-alone group, Cisp-alone group and three rhEPO+Cisp-groups (pre-, co- and post-treatment condition, respectively). Our results show that Cisp induced a noticeable genotoxic effect in rat bone-marrow cells. In all types of treatment, rhEPO significantly decreased the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage. The protective effect of rhEPO was more efficient when it was administrated 24h before exposure to Cisp.
