Effect of glutamine on the initiation and promotion phases of DMBA-induced mammary tumor development.
BACKGROUND
Oral glutamine (GLN) has been shown to up-regulate tissue glutathione (GSH), augment natural killer (NK) cell activity, and prevent tumor growth in an implantable breast cancer model (MTF-7). We hypothesized that dietary GLN would likewise antagonize the induction or promotion of tumor formation by 7,12-dimethylbenz[a]anthracene (DMBA) via up-regulation of GSH or augmentation of NK activity.


METHODS
At age 55 days, 81 Sprague-Dawley rats were gavaged with a one-time dose of 80 mg/kg DMBA, time 0. Rats were randomized into 3 groups (GLN+DMBA, Freamine [FA]+DMBA, water (H2O)+DMBA), pair-fed chow, and gavaged with 1.0 g/kg/day GLN or isonitrogenous amount of FA or H2O for the indicated times: PreFed (-1 to + 16 weeks), Short-Fed (-1 to + 1 weeks) and PostFed (+ 1 to +16 weeks). After 16 weeks, rats were killed and examined for mammary tumors, blood was assayed for GLN and GSH content, and spleens were assayed for NK cytotoxicity.


RESULTS
Over the 4-month study period, there was no significant difference in tumorigenesis between FA and H2O groups, regardless of timing of feeding and amino acid diet, except GLN. In Pre- and PostFed GLN groups, there was no significant difference between groups, but there were significant decreases in tumorigenesis in GLN groups compared with either FA or H2O groups. However, in the Short-Fed group, there was no significant difference in tumorigenesis from the GLN, FA, or H2O groups.


CONCLUSIONS
Continuously supplemented GLN significantly reduced DMBA-induced breast cancer growth when compared with the non-GLN-supplemented and Short-Fed supplemental GLN groups. Furthermore, GLN appears to have its primary effect on promotion and not initiation of tumor formation. This decreased tumor formation was associated with significantly higher arterial GLN and GSH levels and NK activity at killing in the GLN+DMBA group. Protein in the presentation of FA did not promote or prevent tumor growth. These data indicate that GLN may be useful in the chemoprevention of breast cancer.
Kaufmann
Yihong
Y
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Kornbluth
Jacki
J
Feng
Zuliang
Z
Fahr
Michael
M
Schaefer
Robert F
RF
Klimberg
V Suzanne
VS
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects* / Q000633:toxicity; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000009:adverse effects* / Q000633:toxicity; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D004573:Electrolytes; D005260:Female; D005947:Glucose; D005973:Glutamine / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D009584:Nitrogen / Q000378:metabolism; D057947:Parenteral Nutrition Solutions; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013223:Statistics as Topic; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D016387:Women's Health
D000596:Amino Acids; D002273:Carcinogens; D004573:Electrolytes; D057947:Parenteral Nutrition Solutions; D012996:Solutions; C545824:amino-acid, glucose, and electrolyte solution; D005973:Glutamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D005978:Glutathione; D005947:Glucose; D009584:Nitrogen