title: What can surrogate tissues tell us about the oxidative stress status of the prostate? A hypothesis-generating in-vivo study.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kaitlyn F
authors.initials: KF
authors.lastname: Whelan
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lu
authors.forename: Eduard
authors.initials: E
authors.lastname: Fridman
authors.forename: Alex
authors.initials: A
authors.lastname: Wolf
authors.forename: Alon
authors.initials: A
authors.lastname: Honig
authors.forename: Gregory
authors.initials: G
authors.lastname: Paulin
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
authors.forename: Jehonathan H
authors.initials: JH
authors.lastname: Pinthus
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D018859:Hair Follicle / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018384:Oxidative Stress; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D014408:Biomarkers, Tumor; D013739:Testosterone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine