Tomato oleoresin inhibits DNA damage but not diethylnitrosamine-induced rat hepatocarcinogenesis.
Various studies have shown that lycopene, a non-provitamin A carotenoid, exerts antioxidant, antimutagenic and anticarcinogenic activities in different in vitro and in vivo systems. However, the results concerning its chemopreventive potential on rat hepatocarcinogenesis are ambiguous. The aim of the present study was to investigate the antigenotoxic and anticarcinogenic effects of dietary tomato oleoresin adjusted to lycopene concentration at 30, 100 or 300 ppm (administered 2 weeks before and during or 8 weeks after carcinogen exposure) on liver of male Wistar rats treated with a single intraperitoneal dose of 20 or 100mg/kg of diethylnitrosamine (DEN), respectively. The level of DNA damage in liver cells and the development of putative preneoplastic single hepatocytes, minifoci and foci of altered hepatocytes (FHA) positive for glutathione S-transferase (GST-P) were used as endpoints. Significant reduction of DNA damage was detected when the highest lycopene concentration was administered before and during the DEN exposure (20mg/kg). However, the results also showed that lycopene consumption did not reduce cell proliferation in normal hepatocytes or the growth of initiated hepatocytes into minifoci positive for GST-P during early regenerative response after 70% partial hepatectomy, or the number and area of GST-P positive FHA induced by DEN (100mg/kg) at the end of week 10. Taken together, the data suggest a chemopreventive effect of tomato oleoresin against DNA damage induced by DEN but no clear effectiveness in initiating or promoting phases of rat hepatocarcinogenesis.
Scolastici
Clarissa
C
Department of Pathology, Faculty of Medicine, São Paulo State University, Botucatu, SP, Brazil.
Lopes
Gisele A D
GA
Barbisan
Luís F
LF
Salvadori
Daisy M F
DM
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; C018620:oleoresins; D004052:Diethylnitrosamine; D005982:Glutathione Transferase