Avaliação de derivados sintéticos da testosterona pelo teste de mutação e recombinação somática (SMART) em Drosophila melanogaster
CHAPTER II: Anabolic steroids are synthetic derivatives of testosterone modified to enhancethe anabolic rather than the androgenic actions of the hormone. There arenumerous side-effects to anabolic steroids, including carcinogenesis.Hemogenin® (HEM) (oximetholone); Deca Durabolin® (DEC) (decanoate ofnandrolon); and Durateston® (DUR) (propionate of testosterone,fenilppropionate of testosterone, isocaproate of testosterone and decanoate oftestosterone) are listed as the more used steroids. This study evaluated thegenotoxic effects of derivatives of testosterone compounds presents in threedrugs by means of the wing spot test of D. melanogaster (Somatic Mutation andRecombination Test ? SMART). Third-instar larvae derivated from standardcross (ST), where flr3 / In(3LR) TM3, ri ppsep l(3)89Aa bx34e e BdS femaleswere mated with mwh males, and high bioactivation cross (HB), where ORR;flr3 / In(3LR) TM3, ri ppsep l(3)89Aa bx34e e BdS females were mated with mwhmales, were treated for approximately 48 h with different concentrations of HEM(0.625; 1.25 e 2.5 mg/mL) in water; DEC (0.15625; 0.3125; 0.625; 1.25 e 2.5mg/mL) and DUR (0.195; 0.39; 0.78; 1.56 e 3.125 mg/mL), in solution of 1%Tween-80 + 3% ethanol in water; like positive control was used urethane (URE0.891 mg/mL), and negative, the respective solvents used. The results obtainedwith the two different crosses were rather similar, and three drugs showed nonmutageniceffects in D. melanogaster somatic cells. CHAPTER III: Stanozolol, commercial name Winstrol® (WIN), is a synthetic derivative oftestosterone, used for the treatment of anemia, hereditary angioedema andused by sportsmen like anabolic-androgenic steroid. This drug interacts withcytocrome P450, forming a high-affinity ligand complex. This study evaluated,by means of wing spot test of Drosophila melanogaster (Somatic Mutation andRecombination Test - SMART), the effects of stanozolol associated withurethane (URE), known genotoxic agent metabolized by cytocrome P450.Third-instar larvae derived from standard cross (ST), where flr3 / In(3LR) TM3,ri ppsep l(3)89Aa bx34e e BdS females were mated with mwh males, and highbioactivation cross (HB), where ORR; flr3 / In(3LR) TM3, ri ppsep l(3)89Aabx34e e BdS females were mated with mwh males, were treated approximately48 h with different concentrations (0.625; 1.25 e 2.5 mg/mL) of WIN isolatedand in association with URE (0.891 mg/mL). The results observed in bothcrosses suggest that WIN at these experimental conditions, showed nonmutageniceffects and combined treatment of WIN and URE displayed,throughout all concentrations assayed, an inhibition of the effects of URE byWIN, probably this effect is a result of the inhibit-interaction among WIN andcytocrome P450. The relactive proportion of this inhibition was proportional tothe concentrations applied. This work proposes the necessity of more studiesabout metabolism of xenobiotcs agents, like EAA, by cytocrome P450 and theirrelation with genotoxicity.
Advisor:Mario Antonio Spano; Sandra Morelli; Lusânia Maria Greggi Antunes; Edson José Fragiorge; Francis de Morais Franco Nunes
School:Universidade Federal de Uberlândia
Source Type:Master's Thesis
Date of Publication:10/23/2007