Is the Photosuturing Agent, Rose Bengal, a Mutagen?

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.

Co-administration of Mixed Steroid Hormones can Enhance the Recovery of Spermatogenesis Damaged by Gossypol Acetic Acid in Adult Rats

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, spermatogenesis steadily declined. However, when rats received combined hormone administration 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).

Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development

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, Kras LA1, as a driver for lung cancer development in mice, we showed for the first time that mice with Kras LA1 and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured cells, we demonstrated that induced expression of oncogenic KRAS G12 V 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.

采用分析方法、毒理学和风险评估研究评估多环芳烃：以石油泄漏后海产品安全为案例

[背景]多环芳香烃(PAHs)是一种大量蔓延的环境化学物质。它们可通过自然和人为过程产生,通常存在于有机介质(包括石油)中。有几种PAHs是有毒的,其中一些还表现出致癌活性。PAHs以含有两个及以上苯环的一系列化学结构为特征,根据它们的来源,可以通过氧化、氮化和烷基化表现出多种侧链修饰。[目的]讨论当代分析方法日益增加的能力,其不仅可以分辨PAHs中不同的化学结构,而且可以识别它们在环境介质中的浓度。本文以深水地平线事故后海产品污染为例,确定由于个别PAHs的分析灵敏度增加而在PAHs风险评估过程中出现的一些问题,并描述其中许多化合物的毒理学文献缺乏的现状。[讨论]PAHs,包括种类繁多的经化学修饰或取代的PAHs,是自然产生的,如果人群暴露于有害水平就可能会遭受健康风险。然而,目前的毒性评估并没有跟上现代分析方法及其对于被替代的PAHs不断增加的检测能力。因此,尽管我们可以在海产品和其他媒介中检测这些化合物,但并没有足够的关于这些化合物的潜在毒性信息,无法将它们用于人类健康风险评估和特征描述。[结论]今后的研究工作应该尝试从战略上填补这一毒理学知识欠缺,从而更好地进行环境介质或食物中关于PAHs的人体健康风险评估。这对于石油泄漏之后的影响尤为重要。