Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants.
BACKGROUND
Dietary antioxidants with yet unproven efficacies in averting prostate cancer (PCa) are widely used in the United States as preventives. Experimental evidence establishing a causal relationship between oxidative and nitrosative stress (OS/NS) and PCa development and showing its modulation by dietary antioxidants would help justify their usage.


METHODS
The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mouse model was used to demonstrate the OS/NS-associated damage, as evident by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE)-protein-adducts and nitrotyrosine (Ntyr), in prostatic premalignant lesions, and to evaluate the antioxidant efficacy of various dietary supplements [natural antioxidant (NAO) from spinach extracts, (-) epigallocatechin-3-gallate (EGCG), or N-acetylcystein (NAC)] during the early PCa development.


RESULTS
We show, for the first time, that oxidative/nitrosative damages of genomic DNA and cellular proteins were discretely localized in premalignant lesions, but not in adjacent morphologically normal epithelia, of TRAMP prostates; these injuries were absent in age-matched nontransgenic littermates. The extent of OS/NS-related injuries correlated well with the tempo of development and prevalence of premalignant lesions in various prostatic lobes and exhibited a clear trend of increase from 12 to 20 weeks of age. Treatment of TRAMP mice with various antioxidants as dietary supplements resulted in differential alleviation of OS/NS-related prostatic injuries. The antioxidant potencies of the dietary supplements did not fully correlate with their documented antiPCa actions, suggest that they may exert additional "nonantioxidant," antitumor effects in this model.


CONCLUSIONS
Our data indicate that in TRAMP mice, OS/NS injuries are likely involved in early prostatic tumorigenesis and can be modulated by various antioxidants.
Tam
Neville N C
NN
Department of Surgery, Division of Urology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Nyska
Abraham
A
Maronpot
Robert R
RR
Kissling
Grace
G
Lomnitski
Liat
L
Suttie
Andrew
A
Bakshi
Shlomo
S
Bergman
Margalit
M
Grossman
Shlomo
S
Ho
Shuk-Mei
SM
D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D004032:Diet; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010101:Oxygen Consumption; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D018724:Spinacia oleracea
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D010936:Plant Extracts