RESUMEN
Nonylphenol (NP) belongs to the metabolites of commercial detergents, which acts as an environmental endocrine disruptor. NP is reported to have multiple toxicity including reproductive toxicity. In present study, we reported the protective effects of melatonin on the NP-exposed oocyte quality. We set up a mouse in vivo model of NP exposure (500 µg/L), by daily drinking and continued feeding for 4 weeks; and we gave a daily dose of melatonin (30 mg/kg) to the NP-exposed mice. Melatonin supplementation restores the development ability of oocytes exposed to NP, and this was due to the reduction of ROS level and DNA damage by melatonin. Melatonin could rescue aberrant mitochondria distribution, mitochondria membrane potential, which also was reflected by ATP content and mtDNA copy number. Moreover, melatonin could restore the RPS3 expression to ensure the ribosome function for protein synthesis, and reduced GRP78 protein level to protect against ER stress and ER distribution defects. We also found that vesicle protein Rab11 from Golgi apparatus was protected by melatonin at the spindle periphery of oocytes of NP-exposed mice, which further moderated LAMP2 for lysosome function. Our results indicate that melatonin protects oocytes from NP exposure through its effects on the reduction of oxidative stress and DNA damage, which might be through its amelioration on the organelles in mice.
Asunto(s)
Melatonina , Animales , Apoptosis , Suplementos Dietéticos , Meiosis , Melatonina/metabolismo , Melatonina/farmacología , Ratones , Oocitos , Estrés Oxidativo , Fenoles , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To establish human bronchial epithelial cell lines over expressing oncogene and to investigate its application in detection of carcinogen-induced cell transformation. METHODS: Mediated by retrovirus infection, human telomerase catalytic subunit, hTERT was introduced into immortal human bronchial epithelial cells (16HBE) and followed by introduction of the oncogenic allele H-Ras(V12), or c-Myc or empty vector, creating cell lines 16HBETR, 16HBETM and 16HBETV, respectively. Biological characteristics of these cell lines including morphology, proliferation, and chromosomal aberration were examined to access whether they were transformed. Soft agar experiment and nude mice subcutaneous injection were performed using pre-transformed 16HBE cells induced by known carcinogens, nickel sulfate (NiSO4) and 7, 8, -dihydrodiol-9, 10-epoxide benzo[a] pyrene (BPDE). RESULTS: With detection of telomerase activity and Western blotting, the expression of target proteins was verified. Thus, the transgenic 16HBE cell lines were successfully established. Cells expressing oncogene H-Ras or c-Myc grew 30.3% or 10.4% faster than control cells. However, these cells failed to form colonies in soft agar or form tumor in nude mice. 16HBETR, 16HBETM cells obtained transformed phenotype at 5 wks, 11 wks, respectively after treatment with BPDE, which are 15 wks and 9 wks earlier than control cells 16HBETV (20 wks). Meanwhile, 16HBETR, 16HBETM cells obtained transformed phenotype at 11 wks, 14 wks, respectively after treatment with nickel sulfate, which are 21 wks and 18 wks earlier than control cells (32 wks). CONCLUSION: With the advantage of shorter latency, transgenic human cell transformation models could be used in potent carcinogen screening and applied to chemical-carcinogenesis mechanism study.
Asunto(s)
Línea Celular , Transformación Celular Neoplásica , Células Epiteliales , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/toxicidad , Animales , Pruebas de Carcinogenicidad , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Expresión Génica , Regulación de la Expresión Génica , Genes myc , Genes ras , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones DesnudosRESUMEN
OBJECTIVE: To study on the inhibitory effects of juice of tomato on the growth of human prostate carcinoma PC-3 cells and its possible mechanism. METHODS: PC-3 cells were treated with the juice of tomato in different concentration (40, 80, 120 ul/ml) for 48h; the proliferation of PC-3 cells were measured by MTT assay, the comet assay was used to measure the DNA damage of PC-3 cells. RESULTS: Juice of tomato could inhibit the proliferation of PC-3 cells, the growth inhibitory rate of experimental groups were significantly higher than that of control group, with very statistical significance; and it could induce the breakage of DNA single strand of PC-3 cells and resulted in comet cells with tail, Rate of DNA tail and the tail length of DNA increased with the increasing of concentration of juice of tomato, showing the obvious dose effect relationship. CONCLUSION: Juice of tomato could lead to DNA damage of PC-3 cells, it was related to that could inhibit the proliferation of PC-3 cells.