Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat.
To test whether carotenoids can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) or by 2-nitropropane (2-NP) in a sequential protocol of hepatocarcinogenesis, male weanling rats were fed for three or four weeks (respectively) diets containing beta-carotene, canthaxanthin, astaxanthin, or lycopene (300 mg/kg diet) or an excess of vitamin A (15,000 retinol equivalents/kg diet) or were treated intraperitoneally with 3-methylcholanthrene. During this period, all rats were injected intraperitoneally with the initiator carcinogen, either 2-NP (6 times at 100 mg/kg body wt) or DEN (once at 100 mg/kg body wt). Three weeks after the termination of carotenoid or vitamin A feeding, the rats received 50 ppm of 2-acetylaminofluorene in their diet for a two-week period, in the middle of which they were subjected to two-thirds partial hepatectomy, and were sacrificed one week later. gamma-Glutamyl transpeptidase- and placental glutathione S-transferase-positive foci were detected in frozen-cut liver sections by histochemical and histoimmunochemical techniques, respectively. None of the treatments tested had any influence on the number and size of preneoplastic liver foci induced by 2-NP, despite a significant incorporation and persistence in the liver of the carotenoids, except astaxanthin, and of supplemental vitamin A. Feeding the rats lycopene significantly decreased the size of gamma-glutamyl transpeptidase- and glutathione S-transferase-positive foci induced by DEN (by 64% and 65%, respectively), as well as the fraction of liver volume occupied by foci (by 84% and 79%, respectively), but did not significantly reduce their number. The other carotenoids, including beta-carotene, exerted no significant effects on DEN-induced preneoplasias. Lycopene does not appear to act through its antioxidant properties, but rather through its modulating effect on the liver enzyme activating DEN, cytochrome P-450 2E1.
Astorg
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P
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France. astorg@dijon.inra.fr
Gradelet
S
S
Bergès
R
R
Suschetet
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D002338:Carotenoids / Q000627:therapeutic use*; D004052:Diethylnitrosamine; D008113:Liver Neoplasms / Q000139:chemically induced / Q000178:diet therapy*; D000077276:Lycopene; D008297:Male; D009595:Nitroparaffins; D011230:Precancerous Conditions / Q000139:chemically induced / Q000178:diet therapy*; D011407:Propane / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D009595:Nitroparaffins; D002338:Carotenoids; D004052:Diethylnitrosamine; C016617:2-nitropropane; D000077276:Lycopene; D011407:Propane