TY - JOUR
T1 - Effect of Glutamine on the Initiation and Promotion Phases of DMBA-Induced Mammary Tumor Development
AU - Kaufmann, Yihong
AU - Kornbluth, Jacki
AU - Feng, Zuliang
AU - Fahr, Michael
AU - Schaefer, Robert F.
AU - Klimberg, V. Suzanne
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003
Y1 - 2003
N2 - 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 (H 2O)+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 H 2O 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.
AB - 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 (H 2O)+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 H 2O 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.
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U2 - 10.1177/0148607103027006411
DO - 10.1177/0148607103027006411
M3 - Article
C2 - 14621122
AN - SCOPUS:1642513486
SN - 0148-6071
VL - 27
SP - 411
EP - 418
JO - Journal of Parenteral and Enteral Nutrition
JF - Journal of Parenteral and Enteral Nutrition
IS - 6
ER -