Departamento de Anatomia, Instituto de Biociências, UNESP - Universidade Estadual Paulista, Botucatu-SP, Brazil.
Departamento de Anatomia, Instituto de Biociências, UNESP - Universidade Estadual Paulista, Botucatu-SP, Brazil ; Programa de Pós-Graduação em Biologia Celular e Estrutural, Instituto de Biologia, Universidade Estadual de Campinas - UNICAMP, Campinas-SP, Brazil.
PLoS One. 2013 Dec 18;8(12):e81676. doi: 10.1371/journal.pone.0081676. eCollection 2013.
Ovarian cancer is the fourth most common cause of cancer deaths among women, and chronic alcoholism may exert co-carcinogenic effects. Because melatonin (mel) has oncostatic properties, we aimed to investigate and characterize the chemical induction of ovarian tumors in a model of ethanol-preferring rats and to verify the influence of mel treatment on the overall features of these tumors. After rats were selected to receive ethanol (EtOH), they were surgically injected with 100 µg of 7,12-dimethyl-benz[a]anthracene (DMBA) plus sesame oil directly under the left ovarian bursa. At 260 days old, half of the animals received i.p. injections of 200 µg mel/100 g b.w. for 60 days. Four experimental groups were established: Group C, rats bearing ovarian carcinomas (OC); Group C+EtOH, rats voluntarily consuming 10% (v/v) EtOH and bearing OC; Group C+M, rats bearing OC and receiving mel; and Group C+EtOH+M, rats with OC consuming EtOH and receiving mel. Estrous cycle and nutritional parameters were evaluated, and anatomopathological analyses of the ovarian tumors were conducted. The incidence of ovarian tumors was higher in EtOH drinking animals 120 days post-DMBA administration, and mel efficiently reduced the prevalence of some aggressive tumors. Although mel promoted high EtOH consumption, it was effective in synchronizing the estrous cycle and reducing ovarian tumor mass by 20%. While rats in the C group displayed cysts containing serous fluid, C+EtOH rats showed solid tumor masses. After mel treatment, the ovaries of these rats presented as soft and mobile tissues. EtOH consumption increased the incidence of serous papillary carcinomas and sarcomas but not clear cell carcinomas. In contrast, mel reduced the incidence of sarcomas, endometrioid carcinomas and cystic teratomas. Combination of DMBA with EtOH intake potentiated the incidence of OC with malignant histologic subtypes. We concluded that mel reduces ovarian masses and the incidence of adenocarcinomas in ethanol-deprived rats.
卵巢癌是女性癌症死亡的第四大常见原因，慢性酗酒可能产生协同致癌作用。由于褪黑素（mel）具有抗肿瘤特性，我们旨在研究并描述乙醇偏好大鼠模型中卵巢肿瘤的化学诱导作用，并验证 mel 处理对这些肿瘤整体特征的影响。在选择大鼠接受乙醇（EtOH）后，将 100µg 7,12-二甲基苯并[a]蒽（DMBA）加芝麻油直接注射到左侧卵巢囊下。在 260 天大时，一半的动物接受 i.p. 注射 200µg mel/100g b.w.，持续 60 天。建立了四个实验组：C 组，卵巢癌（OC）大鼠；C+EtOH 组，自愿饮用 10%（v/v）EtOH 的大鼠，患有 OC；C+M 组，患有 OC 并接受 mel 治疗的大鼠；和 C+EtOH+M 组，患有 OC 并饮用 EtOH 和接受 mel 的大鼠。评估发情周期和营养参数，并对卵巢肿瘤进行解剖病理学分析。在 DMBA 给药后 120 天，饮用 EtOH 的动物中卵巢肿瘤的发生率更高，而 mel 有效地降低了一些侵袭性肿瘤的患病率。尽管 mel 促进了 EtOH 的高消耗，但它在同步发情周期和减少 20%的卵巢肿瘤质量方面是有效的。在 C 组中，大鼠的卵巢显示含有浆液的囊肿，而 C+EtOH 组的大鼠显示出实性肿瘤。在用 mel 治疗后，这些大鼠的卵巢呈现出柔软且移动的组织。EtOH 消耗增加了浆液性乳头状癌和肉瘤的发生率，但不增加透明细胞癌。相反，mel 降低了肉瘤、子宫内膜样癌和囊性畸胎瘤的发生率。DMBA 与 EtOH 摄入的组合增强了缺乏乙醇的大鼠中 OC 的恶性组织学亚型的发生率。我们得出结论，mel 减少了乙醇剥夺大鼠的卵巢肿块和腺癌的发生率。
