Avaliação de derivados sintéticos da testosterona pelo teste de mutação e recombinação somática (SMART) em Drosophila melanogaster

Abstract

CHAPTER II: Anabolic steroids are synthetic derivatives of testosterone modified to enhance the anabolic rather than the androgenic actions of the hormone. There are numerous side-effects to anabolic steroids, including carcinogenesis. Hemogenin® (HEM) (oximetholone); Deca Durabolin® (DEC) (decanoate of nandrolon); and Durateston® (DUR) (propionate of testosterone, fenilppropionate of testosterone, isocaproate of testosterone and decanoate of testosterone) are listed as the more used steroids. This study evaluated the genotoxic effects of derivatives of testosterone compounds presents in three drugs by means of the wing spot test of D. melanogaster (Somatic Mutation and Recombination Test SMART). Third-instar larvae derivated from standard cross (ST), where flr3 / In(3LR) TM3, ri ppsep l(3)89Aa bx34e e BdS females were 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 mwh males, 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 2.5 mg/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 (URE 0.891 mg/mL), and negative, the respective solvents used. The results obtained with the two different crosses were rather similar, and three drugs showed nonmutagenic effects in D. melanogaster somatic cells. CHAPTER III: Stanozolol, commercial name Winstrol® (WIN), is a synthetic derivative of testosterone, used for the treatment of anemia, hereditary angioedema and used by sportsmen like anabolic-androgenic steroid. This drug interacts with cytocrome P450, forming a high-affinity ligand complex. This study evaluated, by means of wing spot test of Drosophila melanogaster (Somatic Mutation and Recombination Test - SMART), the effects of stanozolol associated with urethane (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 high bioactivation cross (HB), where ORR; flr3 / In(3LR) TM3, ri ppsep l(3)89Aa bx34e e BdS females were mated with mwh males, were treated approximately 48 h with different concentrations (0.625; 1.25 e 2.5 mg/mL) of WIN isolated and in association with URE (0.891 mg/mL). The results observed in both crosses suggest that WIN at these experimental conditions, showed nonmutagenic effects and combined treatment of WIN and URE displayed, throughout all concentrations assayed, an inhibition of the effects of URE by WIN, probably this effect is a result of the inhibit-interaction among WIN and cytocrome P450. The relactive proportion of this inhibition was proportional to the concentrations applied. This work proposes the necessity of more studies about metabolism of xenobiotcs agents, like EAA, by cytocrome P450 and their relation with genotoxicity.