Effects of dietary energy repletion and IGF-1 infusion on the inhibition of mammary carcinogenesis by dietary energy restriction

Mol Carcinog. 2005 Mar;42(3):170-6. doi: 10.1002/mc.20071.


Dietary energy restriction (DER) is a potent inhibitor of mammary carcinogenesis, but the responsible mechanisms are not fully understood. In a number of model systems, DER is associated with a decrease in circulating levels of IGF-1. Moreover, we have recently reported that protection against cancer is lost, and plasma IGF-1 levels are restored to control values when animals are re-fed, i.e., energy repleted (DER-REP). Accordingly, an experiment was designed to determine if infusion of IGF-1 could mimic the effect of DER-REP on the carcinogenic response in animals that were DER. Following 1-methyl-1-nitrosourea injection (50 mg/kg), rats were fed either ad libitum (AL) or 40% DER. After 6 wk, the DER group was divided into three groups: (1) continued DER, (2) DER-REP, or (3) continued DER and infused with 120 mug rh-IGF-1/d (INF) for a duration of 8 d. DER reduced mammary cancer incidence and multiplicity (P < 0.01) versus AL rats. In rats that were DER-REP, cancer incidence increased 1.4-fold and multiplicity increased by 3.6-fold versus DER rats. Plasma IGF-1 were reduced by DER (P < 0.01), an effect that was reversed by DER-REP (P < 0.05). INF increased plasma IGF-1 versus DER rats (P < 0.01) but did not reverse the carcinogenic response. Plasma IGFBP-3 levels were reduced by DER (P < 0.01), but elevated by either REP or INF. Thus, an 8-d period of refeeding following chronic DER (DER-REP) reversed the anticancer effects of DER, and 8 d of IGF-1 infusion without refeeding (INF) did not mimic the effects of the DER-REP on the carcinogenic response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Caloric Restriction*
  • Carcinogens
  • Cell Transformation, Neoplastic / chemically induced
  • Corticosterone / blood
  • Energy Intake
  • Female
  • Glucose / metabolism
  • Growth Hormone / blood
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor I / physiology
  • Mammary Neoplasms, Animal / chemically induced*
  • Mammary Neoplasms, Animal / diet therapy*
  • Mammary Neoplasms, Animal / metabolism
  • Methylnitrosourea
  • Rats
  • Rats, Sprague-Dawley


  • Blood Glucose
  • Carcinogens
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Methylnitrosourea
  • Growth Hormone
  • Glucose
  • Corticosterone