Abstract

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.

摘要

黑色素瘤是一种源自黑色素细胞的侵袭性皮肤癌，可转移至肺、肝、皮质、股骨和脊髓，最终导致 DNA 诱变效应。褪黑激素是一种内源性激素和自由基清除剂，具有保护 DNA 和在黑色素瘤细胞中发挥抗增殖作用的能力。本研究的目的是评估 B16F10 黑色素瘤细胞的影响以及补充褪黑激素对小鼠黑色素瘤模型中遗传毒性参数的影响。将 32 只雄性 C57Bl/6 小鼠分为以下四组：PBS + 载体（n  = 6）、黑色素瘤 + 载体（n  = 10）、PBS + 褪黑素（n  = 6）和黑色素瘤 + 褪黑素（n = 10)。黑色素瘤组接受 B16F10 细胞注射，并在 60 天内给予褪黑激素。治疗后，评估肿瘤大小。外周血、肺、肝、皮质和脊髓内的DNA损伤采用彗星试验测定，骨髓内的致突变性采用微核试验测定。B16F10 细胞有效诱导所有组织中的 DNA 损伤，补充褪黑激素可减少血液、肝脏、皮质和脊髓中的 DNA 损伤。这种激素通过其抗增殖、抗氧化和促凋亡作用发挥抗肿瘤活性。由于在肺内没有观察到这一结果，我们假设褪黑激素可以诱导癌细胞凋亡，这没有通过彗星试验进行评估。