Effects of dietary energy repletion and IGF-1 infusion on the inhibition of mammary carcinogenesis by dietary energy restriction.
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.
Zhu
Zongjian
Z
Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado 80523, USA.
Jiang
Weiqin
W
McGinley
John
J
Wolfe
Pamela
P
Thompson
Henry J
HJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D031204:Caloric Restriction; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D003345:Corticosterone / Q000097:blood; D002149:Energy Intake; D005260:Female; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000178:diet therapy* / Q000378:metabolism; D008770:Methylnitrosourea; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002273:Carcinogens; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D008770:Methylnitrosourea; D013006:Growth Hormone; D005947:Glucose; D003345:Corticosterone