Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat

Nutr Cancer. 1997;29(1):60-8. doi: 10.1080/01635589709514603.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Carcinogens
  • Carotenoids / therapeutic use*
  • Diethylnitrosamine
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / diet therapy*
  • Lycopene
  • Male
  • Nitroparaffins
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / diet therapy*
  • Propane / analogs & derivatives
  • Rats
  • Rats, Wistar


  • Anticarcinogenic Agents
  • Carcinogens
  • Nitroparaffins
  • Carotenoids
  • Diethylnitrosamine
  • 2-nitropropane
  • Lycopene
  • Propane