Liver tumorigenicity of trimethylarsine oxide in male Fischer 344 rats--association with oxidative DNA damage and enhanced cell proliferation

Problem To determine if epidermal cell proliferation in colony-raised Fischer 344 rats changes with age and diet. Methods Fischer 344 rats fed ad libitum and calorie-restricted (CR) diets were obtained from the NIA colonies, and young, young adult, and old animals from both groups were used for this study (six in each group). Tissue sections from the dorsal skin (DS) and foot plate (FP) were used for immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The proliferation index (PCNA-I) was computed from counts of stained and total number of keratinocytes. Simultaneous measurements of epidermal thickness were obtained from same sections. Data were analyzed with Excel and SPSS 14.0 software for statistics. Results Two-way analysis of variance (ANOVA) was applied to the data to probe the effect of age, diet, and age-diet interaction. A significant effect of age was noticed in the two parameters i.e., DS PCNA (F 3.96, P .011), FP epidermal width (F 3.37, P .021) and FP PCNA-I (F 9.0, P .000). A significant correlation between DS width and PCNA values was also noted (r 0.5, P .01). Conclusion There is a trend of reduction of PCNA positive cells with increasing age irrespective of thickness of epidermis, and this trend is more apparent in CR rats. Significance This cell proliferation study has implications in relation to CR effect on age-related disease conditions, and biogerontology. Support The study was partially funded by the 2007 Leslie Bernstein grant from AAFPRS foundation.

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The oxidative effect of Hyperbaric Oxygen Therapy on Human retinal pigment epithelium cells

10.21203/rs.2.14558/v1 ◽

2019 ◽

Author(s):

Jialin Li ◽

I-Chen Chao ◽

Jie Luan

Keyword(s):

Cell Proliferation ◽

Dna Damage ◽

Retinal Pigment Epithelium ◽

Hyperbaric Oxygen ◽

Oxidative Dna Damage ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Control Group ◽

Rpe Cells ◽

Human Retinal Pigment Epithelium

Abstract Background: Hyperbaric oxygen (HBO) therapy has been widely used in various diseases, which is considered safe and effective. Whereas recent studies discovered that HBO therapy could result in oxidative damage to tissues. The goal of our study was to investigate the oxidative effect of hyperbaric oxygen therapy on human retinal pigment epithelium (RPE) cells. Method: Human REP cells (ARPE-19) were cultured in vitro, and divided into normoxic group （incubated with DMEM/F12 broth）and hypoxic group (incubated with DMEM/F12 broth containing 200μmol/L CoCl2) randomly. The experimental groups were exposed to 100% pure oxygen under different pressures (0.15MPa, 0.2MPa, and 0.25MPa) for 60 and 90 minutes thrice, with 24 hours interval. Then the cell viability, 8-OHdG expression and hOGG1 expression of RPE cells were detected by MTT assay, immunocytochemistry (ICC) and western blot seperately. Result: After HBO exposure, cell proliferation decreased, 8-OHdG and hOGG1 expression increased in normoxic RPE cells compared with control group, whereas in hypoxic RPE cells, cell proliferation increased, 8-OHdG and hOGG1 expression decreased compared with hypoxic control group. Conclusion: HBO therapy could suppress the cell proliferation and cause oxidative DNA damage of RPE cells in normoxic status. Conversely, in hypoxic status, HBO therapy could promote the proliferation and ameliorate oxidative DNA damage of human retinal pigment epithelium cells. Meanwhile, HBO therapy could trigger the oxidative DNA damage repair of RPE cells in both normoxic and hypoxic statues.

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