Effect of glutamine on glutathione, IGF-I, and TGF-beta 1.
BACKGROUND
Our previous results have showed that oral glutamine (GLN) supplementation decreased carcinogenesis in 7,12-dimethylbenz[a]antracene (DMBA) breast cancer model. We also have found that GLN raises blood glutathione (GSH) levels in an implantable breast cancer model. The process of tumor growth was accompanied by depressed GSH production and increased levels of insulin-like growth factor-I (IGF-I) and transforming growth factor beta1 (TGF-beta 1). GSH is counter-regulatory to IGF-I. We therefore hypothesized that in DMBA model of breast cancer, the increased GSH levels seen with oral GLN would be associated with lowered levels of IGF-I &TGF-beta(1).


METHODS
Time-dated pubertal Sprague-Dawley rats were gavaged at time 0 with 1 g/kg/day glutamine (GLN) (n = 18), isonitrogenous Freamine (FA) (n = 18), or water (H(2)O) (n = 18). Rats were further randomized on day 7 to 100 mg/kg DMBA or oil. After 14 days, the animals were sacrificed and blood GSH, IGF-1, TGF-beta 1, breast tissue, and gut mucosa GSH levels were measured.


RESULTS
Oral GLN increased significantly blood, breast tissue, and gut mucosa levels of GSH in both DMBA and control groups in comparison with the control groups not treated with GLN. At the same time, the levels of blood IGF-I and TGF-beta 1 decreased significantly in both DMBA-treated and control groups. DMBA did not significantly affect any of these levels. CONCLUSIONS ;Oral GLN increased GSH levels and lowered IGF-I and TGF-beta 1 in a range that is considered clinically significant. However, the effect of GLN in maintaining normal gut GSH production in the presence of DMBA was much more significant. Inconsistent with our hypothesis, reduction in IGF and TGF-beta 1 levels did not correlate with DMBA's effect on gut GSH production.
Johnson
Anita T
AT
University of Arkansas for Medical Sciences, Division of Breast Surgical Oncology, Little Rock, Arkansas 72205, USA.
Kaufmann
Yihong Cao
YC
Luo
Shaoke
S
Todorova
Valentina
V
Klimberg
V Suzanne
VS
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage; D000818:Animals; D001158:Arteries; D001940:Breast / Q000737:chemistry; D004032:Diet; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D005978:Glutathione / Q000032:analysis* / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007413:Intestinal Mucosa / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005973:Glutamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D005978:Glutathione