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Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants
Author(s) -
Tam Neville N.C.,
Nyska Abraham,
Maronpot Robert R.,
Kissling Grace,
Lomnitski Liat,
Suttie Andrew,
Bakshi Shlomo,
Bergman Margalit,
Grossman Shlomo,
Ho ShukMei
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20313
Subject(s) - tramp , oxidative stress , prostate cancer , antioxidant , medicine , nitrotyrosine , prostate , cancer , oxidative phosphorylation , endocrinology , physiology , pathology , cancer research , biology , biochemistry , nitric oxide synthase , nitric oxide
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 ( Tr ansgenic A denocarcinoma of the M ouse P rostate) 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. RESULT 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. © 2005 Wiley‐Liss, Inc.