title: Lutein presents suppressing but not blocking chemopreventive activity during diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of DNA damage.
abstract: Cancer chemopreventive agents are classified as blocking or suppressing agents if they inhibit initiation or promotion/progression phase of carcinogenesis, respectively. Two experiments were conducted in order to classify lutein as a blocking and/or suppressing agent during rat hepatocarcinogenesis. Inhibitory effects of lutein on hepatic preneoplastic lesions (PNL) and DNA strand breakage induced in Wistar rats by the resistant hepatocyte model of hepatocarcinogenesis (initiation with diethylnitrosamine and promotion with 2-acetylaminofluorene coupled with partial hepatectomy) were investigated when the carotenoid was administered specifically during initiation (experiment 1) or promotion (experiment 2) phase. Animals received by gavage during 2 (experiment 1) or six (experiment 2) consecutive weeks on alternate days 70 mg/kg body weight of lutein. Rats treated with only corn oil during these same periods and submitted to this model were used as controls. Treatment with lutein during initiation did not inhibit nor induced (P>0.05) hepatic preneoplastic lesions and DNA damage. On the other hand, treatment during promotion inhibited (P<0.05) the size of hepatic macroscopic nodules and DNA damage and increased (P<0.05) lutein hepatic levels that reached levels seen in human liver samples. Lutein presented inhibitory actions during promotion but not initiation of hepatocarcinogenesis, being classified as a suppressing agent. This reinforces lutein as a potential agent for liver cancer chemoprevention.
authors.affiliation: Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes 580, Bloco 14, 05508-900 São Paulo, SP, Brazil.
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
authors.forename: Luciana Passos
authors.initials: LP
authors.lastname: Toledo
authors.forename: Aline
authors.initials: A
authors.lastname: de Conti
authors.forename: Renato
authors.initials: R
authors.lastname: Heidor
authors.forename: Alceu
authors.initials: A
authors.lastname: Jordão
authors.forename: Hélio
authors.initials: H
authors.lastname: Vannucchi
authors.forename: Mônica Testoni
authors.initials: MT
authors.lastname: Cardozo
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D004249:DNA Damage / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D014975:Lutein / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D004052:Diethylnitrosamine; D014975:Lutein