Carcinogenesis Advance Access published online on June 23, 2005
Carcinogenesis, doi:10.1093/carcin/bgi161
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1 Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
* To whom correspondence should be addressed. Chemopreventive activities of all-trans retinoic acid (AtRA), 9-cis retinoic acid (9cRA), retinol (ROL) and
Received March 17, 2005
Revised June 10, 2005
Accepted June 15, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
All-trans and 9-cis retinoic acids, retinol and
-carotene chemopreventive activities during the initial phases of hepatocarcinogenesis involve distinct actions on glutathione S-transferase positive preneoplastic lesions remodeling and DNA damage
Fernando Salvador Moreno, E-mail: RMORENO{at}USP.BR
Abstract 
-carotene (C) were evaluated during hepatocarcinogenesis. Rats received 1 mg/100 g body weight AtRA (AtRA group), 9cRA (9cRA group), ROL (ROL group), 7 mg/100 g body weight C (C group) or corn oil (CO group, controls). Hepatocyte nodule incidence was reduced (P < 0.05) in C group (46%), but not (P > 0.05) in AtRA (92%), 9cRA (92%) and ROL (82%) groups, compared to CO group (100%). Multiplicity of these preneoplastic lesions (PNL) was different (P < 0.05) between CO group (44±9) and 9cRA (11±4), ROL (7±3) and C (4±2) groups, except for AtRA group (27±9; P > 0.05). Number/cm2 liver section, mean area (mm2) and % liver section area occupied by total (persistent + remodeling) placental glutathione S-transferase (GST-P) positive PNL was reduced (P < 0.05) in AtRA (107±13; 0.12±0.06; 13.9±3.9), 9cRA (71±12; 0.12±0.06; 6.8±2.2), ROL (96±13; 0.11±0.22; 6.8±2.0) and C (106±13; 0.08±0.03; 10.8±2.5) groups compared to CO group (166±14; 0.18±0.09; 28.6±5.2). % of remodeling GST-P positive PNL was increased (P < 0.05) in 9cRA (92±1), ROL (96±1) and C (93±1) groups, but not (P > 0.05) in AtRA group (90±2), compared to CO group (86±1). Compared to CO group, all groups present in PNL reduced (P < 0.05) cell proliferation and no differences (P > 0.05) in apoptosis. DNA damage [comet length (µm)] was reduced (P < 0.05) in ROL (87.9±2.6) and C (89.2±4.0) groups, but not in AtRA (94.8±4.1) and 9cRA (94.2±1.5) groups, compared to CO group (100.4±3.9). AtRA, 9cRA, ROL and C presented chemopreventive activities against hepatocarcinogenesis. These involve inhibition of cell proliferation, but not induction of apoptosis. Increased remodeling of GST-P positive PNL relates to 9cRA, ROL and C actions, while inhibition of DNA damage relates to ROL and C actions.
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