Rose Bengal (RB) is a potential photosuturing agent that may improve standard dermatologic surgical closure techniques. However, RB produces reactive oxygen species with photoactivation and its photomutagenic potentia...Rose Bengal (RB) is a potential photosuturing agent that may improve standard dermatologic surgical closure techniques. However, RB produces reactive oxygen species with photoactivation and its photomutagenic potential must be considered in clinical application. We investigated cytotoxicity, mutagenicity, and singlet oxygen (SO) production of RB on epithelial Chinese hamster ovary cell line. Cells were exposed to RB concentrations: 0.1%, 0.01%, 0.001%, 0.0001%, 0.00001%;irradiated for 400 s using a high-intensity visible wavelength lamp or maintained in the dark. Cell viability was assessed by XTT assay, mutagenicity by HPRT gene mutation assay, and SO production by Sensor Green reagent. RB > 0.001% was significantly cytotoxic. Viabilities were uninfluenced by ≤0.0001% RB controls, or 30-min incubation. 49% of irradiated cells died after 24-h in 0.0001% RB. At ≥0.001% RB, >90% of cells died. Irradiating 0.00001% - 0.001% RB increased SO;levels dropped significantly between 0.01% - 0.1%. Controls exhibited negligible SO production. HPRT suggested that RB was not mutagenic (0.0001%, 0.00001%);SO induction increased between 0.00001% - 0.001%, with reduced production at higher concentrations. Pilot studies suggested irradiated 0.0001% RB is mutagenic in vitro;current data suggest RB is not photomutagenic. The contribution of RB’s cytotoxicity on observed clinical improvement of scars and mutagenic potential remains unclear, necessitating further study.展开更多
Objective To determine whether co-administration of mixed steriod hormones can enhance the restoration of spermatogenesis damaged by gossypol acetic acid （GA）. Methods Adult male Wistar rats were treated daily for 8...Objective To determine whether co-administration of mixed steriod hormones can enhance the restoration of spermatogenesis damaged by gossypol acetic acid （GA）. Methods Adult male Wistar rats were treated daily for 8 weeks with GA at 50mg/kg plus testosterone undercanoate （100 mg/kg）/desogestrel （0.125 mg/kg）/mini-dose ethinylestradiol （0.025 mg/kg） （TU/DSG/EE）, followed by a period of 9 weeks for recovery. Control animals were administered the same dose of GA or TU/DSG/EE, and vehicle, respectively. Testis weight, testicular sperm head count and histological analysis were utilized to assess the spermatogenesis. Results At the end of the 9-week reovery period, in rats given GA alone, spermato- genesis steadily declined. However, when rats received combined hormone adminis- tration during GA treatment, this decline was prevented and an complete recovery of spermagenesis occurred. The haploid spermatids and spermatocytes was not to be protected but to be more aggravatedly damaged. The excellent recovery must have resulted from that the hormone treatment could protect the ability of stem spermatogonia to differentialte and evolve progressively into mature spermatozoa. In addition, the concentrations of serum LH, FSH and intratesticular testosteron （ITT） notably decreased after 2 or 8 weeks of treatment, then returned to control levels at the end of 9-week recovery period.Conclusion Steriod hormone treatment enhaces the recovery of spermatogenesis through preventing seminiferous epithelim from GA-induced destructive damage in rats. The enhanced recovery was closely associated with the marked suppression in intratesticular testosteron （ITT）.展开更多
Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer wo...Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C （XPC） are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog （Kras） or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, KrasTM, as a driver for lung cancer development in mice, we showed for the first time that mice with KrasTM and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured ceils, we demonstrated that induced expression of oncogenic KR.ASG12v led to increased levels of reactive oxygen species （ROS） as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS.展开更多
文摘Rose Bengal (RB) is a potential photosuturing agent that may improve standard dermatologic surgical closure techniques. However, RB produces reactive oxygen species with photoactivation and its photomutagenic potential must be considered in clinical application. We investigated cytotoxicity, mutagenicity, and singlet oxygen (SO) production of RB on epithelial Chinese hamster ovary cell line. Cells were exposed to RB concentrations: 0.1%, 0.01%, 0.001%, 0.0001%, 0.00001%;irradiated for 400 s using a high-intensity visible wavelength lamp or maintained in the dark. Cell viability was assessed by XTT assay, mutagenicity by HPRT gene mutation assay, and SO production by Sensor Green reagent. RB > 0.001% was significantly cytotoxic. Viabilities were uninfluenced by ≤0.0001% RB controls, or 30-min incubation. 49% of irradiated cells died after 24-h in 0.0001% RB. At ≥0.001% RB, >90% of cells died. Irradiating 0.00001% - 0.001% RB increased SO;levels dropped significantly between 0.01% - 0.1%. Controls exhibited negligible SO production. HPRT suggested that RB was not mutagenic (0.0001%, 0.00001%);SO induction increased between 0.00001% - 0.001%, with reduced production at higher concentrations. Pilot studies suggested irradiated 0.0001% RB is mutagenic in vitro;current data suggest RB is not photomutagenic. The contribution of RB’s cytotoxicity on observed clinical improvement of scars and mutagenic potential remains unclear, necessitating further study.
基金supported by the National Natural Science Foundation of China (30760267)The grants under Inner Mongolia Health & Medical development foundation (2006-033)+1 种基金Colleges and Universities Scientific Research Projects of Inner Mongolia Education Department (NJ06015)Health and Medical Development Foundation of Baotou (20060-28)
文摘Objective To determine whether co-administration of mixed steriod hormones can enhance the restoration of spermatogenesis damaged by gossypol acetic acid （GA）. Methods Adult male Wistar rats were treated daily for 8 weeks with GA at 50mg/kg plus testosterone undercanoate （100 mg/kg）/desogestrel （0.125 mg/kg）/mini-dose ethinylestradiol （0.025 mg/kg） （TU/DSG/EE）, followed by a period of 9 weeks for recovery. Control animals were administered the same dose of GA or TU/DSG/EE, and vehicle, respectively. Testis weight, testicular sperm head count and histological analysis were utilized to assess the spermatogenesis. Results At the end of the 9-week reovery period, in rats given GA alone, spermato- genesis steadily declined. However, when rats received combined hormone adminis- tration during GA treatment, this decline was prevented and an complete recovery of spermagenesis occurred. The haploid spermatids and spermatocytes was not to be protected but to be more aggravatedly damaged. The excellent recovery must have resulted from that the hormone treatment could protect the ability of stem spermatogonia to differentialte and evolve progressively into mature spermatozoa. In addition, the concentrations of serum LH, FSH and intratesticular testosteron （ITT） notably decreased after 2 or 8 weeks of treatment, then returned to control levels at the end of 9-week recovery period.Conclusion Steriod hormone treatment enhaces the recovery of spermatogenesis through preventing seminiferous epithelim from GA-induced destructive damage in rats. The enhanced recovery was closely associated with the marked suppression in intratesticular testosteron （ITT）.
基金supported by National Cancer Institute (Nos. R01CA155086 and R01CA94160) to J. Xie,National Institute of Environmental Sciences (No. RO1 ES018948) to I. Boldorgh
文摘Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C （XPC） are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog （Kras） or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, KrasTM, as a driver for lung cancer development in mice, we showed for the first time that mice with KrasTM and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured ceils, we demonstrated that induced expression of oncogenic KR.ASG12v led to increased levels of reactive oxygen species （ROS） as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS.
