Chemico-Biological Interactions 168 (2007) 221–228 Lutein presents suppressing but not blocking chemopreventive activity during diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of DNA damage Fernando Salvador Moreno a , Luciana Passos Toledo a , Aline de Conti a , Renato Heidor a , Alceu Jord˜ ao Jr. b , H´ elio Vannucchi b , Mˆ onica Testoni Cardozo a , Thomas Prates Ong a,∗ a Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of S˜ ao Paulo, Av. Professor Lineu Prestes 580, Bloco 14, 05508-900 S˜ ao Paulo, SP, Brazil b Nutrition Division, Department of Clinical Medicine, Faculty of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeir ˜ ao Preto, SP, Brazil Received 23 January 2007; received in revised form 17 April 2007; accepted 18 April 2007 Available online 4 May 2007 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. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Hepatocarcinogenesis; Chemoprevention; Lutein; Blocking agent; Suppressing agent; DNA damage 1. Introduction Primary liver cancer is the fifth most common can- cer in the world and the third most common cause of ∗ Corresponding author. Tel.: +55 11 3091 3630; fax: +55 11 3815 4410. E-mail address: tong@usp.br (T.P. Ong). cancer mortality. Almost 560,000 cases are diagnosed each year and 550,000 deaths due to liver cancer occur mainly in developing countries [1]. In view of the limited treatment and negative prognosis for the disease, preven- tive control approaches, notably chemoprevention, have been emphasized [2]. Initiation, promotion and progression of carcino- genesis involve a continuous oxidative state that can 0009-2797/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.cbi.2007.04.011