Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2010 Dec 28;5(12):e15880. doi: 10.1371/journal.pone.0015880.
Prostatic oxidative stress (OS) is androgen-regulated and a key event in the development of prostate cancer (PC). Thus, reducing prostatic OS is an attractive target for PC prevention strategies. We sought to determine if the individual's prostatic OS status can be determined by examining the OS in surrogate androgen regulated tissues from the same host.
METHODOLOGY/PRINCIPAL FINDINGS: Adult male rats were divided equally into three groups: (A-) underwent bilateral orchiectomy, (A+) received continuous testosterone supplementation or (C) were eugonadal. Serum testosterone, 8-hydroxy-2-deoxyguanosine (8-OHdG) and anti-oxidative capacity (AOC) were determined after 72 hrs and the prostate, salivary glands and the hair follicles' Dermal Papillary Cells (DPC) from each animal were harvested, embedded into tissue microarray and examined for the expression of 8-OHdG by immuno-staining. Multi-variate regression was used to analyze inter-individual differences in OS staining within each androgen group and if there was a correlation between serum testosterone, 8-OHdG or AOC and Prostatic OS in tissues of same host. At the group level, 8-OHdG staining intensity directly correlated with serum testosterone levels in all three target tissues (p>0.01, Mann-Whitney Test). Although different levels of prostatic OS were noted between rats with similar serum testosterone levels and similar systemic OS measurements (p<0.01), there were no intra-individual differences between the OS status of the prostate and DPC (p<0.05).
CONCLUSIONS/SIGNIFICANCE: The level of prostatic OS is correlated with the OS of hair follicles and salivary glands, but not systemic OS. Moreover, systemic AOC negatively correlates with both prostatic and hair follicle OS. This suggests that hair follicle and salivary gland OS can serve as surrogate markers for the efficiency of OS reduction. This has tremendous potential for the rational evaluation of patient response to prevention strategies.
前列腺氧化应激（OS）受雄激素调控，是前列腺癌（PC）发展的关键事件。因此，降低前列腺 OS 是预防 PC 策略的一个有吸引力的目标。我们试图确定是否可以通过检查同一宿主的雄激素调节组织中的 OS 来确定个体的前列腺 OS 状态。
方法/主要发现：成年雄性大鼠等分为三组：（A-）行双侧睾丸切除术，（A+）接受持续的睾酮补充或（C）为正常生育力。在 72 小时后测定血清睾酮、8-羟基-2-脱氧鸟苷（8-OHdG）和抗氧化能力（AOC），从每只动物中采集前列腺、唾液腺和毛囊的真皮乳头细胞（DPC），嵌入组织微阵列中，并通过免疫染色检查 8-OHdG 的表达。多元回归用于分析每个雄激素组内个体间 OS 染色的差异，以及血清睾酮、8-OHdG 或 AOC 与同一宿主组织中前列腺 OS 是否存在相关性。在组水平上，所有三种靶组织中，8-OHdG 染色强度与血清睾酮水平直接相关（p>0.01，Mann-Whitney 检验）。尽管在具有相似血清睾酮水平和相似系统性 OS 测量值的大鼠之间观察到前列腺 OS 水平存在差异（p<0.01），但前列腺和 DPC 的 OS 状态之间没有个体内差异（p<0.05）。
结论/意义：前列腺 OS 水平与毛囊和唾液腺的 OS 相关，但与系统性 OS 无关。此外，系统性 AOC 与前列腺和毛囊 OS 均呈负相关。这表明毛囊和唾液腺 OS 可以作为 OS 降低效率的替代标志物。这为合理评估患者对预防策略的反应提供了巨大潜力。
