Avaliação genotóxica da hidroxiuréia em células somáticas de Drosophila melanogaster

Abstract

Hydroxyurea (HU) was synthesized in Germany in 1869 by Dresler and Stein, but only in 1928 was its biological activity demonstrated in rabbit experiments due to the presence of leukopenia, anemia and bone marrow changes in these animals (Rosenthal et al. ., 1928 apud Timson, 1975). Between 1960 and 1970 a series of studies and case reports documented UH activity in psoriasis and a variety of hematological conditions (Kennedy and Yarbro, 1966; Leavell and Yarbro, 1970). In one of these reports, it was shown that HU had antitumor activity against sarcoma 180, which aroused interest in the compound as a possible antineoplastic agent. (Stock et al., 1960). UH is used in the treatment of myeloproliferative disorders (Malpas, 1967; Weil and Tanzer, 1967), hypereosinophilic syndrome (Parrillo et al., 1978), metastatic malignant melanoma, solid tumors (Becloff, 1967), HIV infections (Lori, 1999; Seminari et al., 1999), hemoglobinopathies, among which stand out sickle cell anemia (Platt et al., 1984; Dover et al., 1986; Charache et al., 1987; Charache, 1996) and beta thalassemia (Fucharoen et al., 1996; Voskaridou etal., 1995). UH is rapidly absorbed in the gastrointestinal tract after oral ingestion and is well distributed throughout the body (Becloff 1967; Blacow 1972). HU reaches peak blood levels one to two hours after administration, penetrates cells by passive diffusion, rapidly enters cerebrospinal fluid, and is excreted in the urine with a half-life of less than eight hours (Donehower, 1982; Yarbro, 1992). ). HU inhibits ribonucleoside diphosphate reductase (NDPR), an enzyme that converts ribonucleotides into deoxyribonucleotide triphosphates (dNTPs) for DNA synthesis and repair (Krakoff et al. 1968; Moore and Hurlbert, 1985), a target enzyme for chemotherapeutic agents.