title: Novel surrogate end-point biomarker to evaluate agents for use in the chemoprevention of reactive oxygen species-associated cancer.
abstract: Cancer chemoprevention is the use of chemical agents to inhibit, delay or reverse carcinogenesis. We established a novel method to evaluate agents for use in the chemoprevention of reactive oxygen species (ROS)-associated cancer. Induction of renal cell carcinoma in rats by ferric nitrilotriacetate (Fe-NTA) is an established model of ROS-associated cancer. We recently identified the p16INK4A tumor suppressor gene as one of the major target genes in this model, and showed by the use of in situ hybridization that allelic loss of p16IK4A occurs in the increased fraction of renal tubular cells within a few weeks. In the present study, we tested whether diets including green tea powder or a processed grain food are effective chemopreventive agents in this animal model. Consumption of these modified diets led to a significant decrease in the fraction of aneuploid cells after 1 week of repeated Fe-NTA administration. A decrease in renal lipid peroxidation after a single administration of Fe-NTA was also observed. Therefore, intake of green tea or processed grain foods stabilizes p16INK4A in the genome, at least in this model, and might be helpful for the prevention of ROS-associated cancer. This novel method is versatile, and may work as a surrogate end-point biomarker for screening the usefulness of agents for cancer chemoprevention.
authors.affiliation: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiroyasu
authors.forename: Munetaka
authors.initials: M
authors.lastname: Ozeki
authors.forename: Aya
authors.initials: A
authors.lastname: Miyagawa-Hayashino
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000483:Alleles; D000818:Animals; D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D015227:Lipid Peroxidation; D008297:Male; D009369:Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances