Effect of Glutamine on the Initiation and Promotion Phases of DMBA-Induced Mammary Tumor Development

Yihong Kaufmann, Jacki Kornbluth, Zuliang Feng, Michael Fahr, Robert F. Schaefer, Vicki Klimberg

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 H 2O 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 H 2O 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 H 2O 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.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
JournalJournal of Parenteral and Enteral Nutrition
Volume27
Issue number6
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

9,10-Dimethyl-1,2-benzanthracene
mammary neoplasms (animal)
Glutamine
glutamine
Breast Neoplasms
neoplasms
breast neoplasms
carcinogenesis
Carcinogenesis
Neoplasms
rats
Up-Regulation
Growth
chemoprevention
Chemoprevention
natural killer cells
Natural Killer Cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Effect of Glutamine on the Initiation and Promotion Phases of DMBA-Induced Mammary Tumor Development. / Kaufmann, Yihong; Kornbluth, Jacki; Feng, Zuliang; Fahr, Michael; Schaefer, Robert F.; Klimberg, Vicki.

In: Journal of Parenteral and Enteral Nutrition, Vol. 27, No. 6, 11.2003, p. 411-418.

Research output: Contribution to journalArticle

Kaufmann, Yihong ; Kornbluth, Jacki ; Feng, Zuliang ; Fahr, Michael ; Schaefer, Robert F. ; Klimberg, Vicki. / Effect of Glutamine on the Initiation and Promotion Phases of DMBA-Induced Mammary Tumor Development. In: Journal of Parenteral and Enteral Nutrition. 2003 ; Vol. 27, No. 6. pp. 411-418.
@article{4bfcf6cd323d4c2cbb0972770e21de07,
title = "Effect of Glutamine on the Initiation and Promotion Phases of DMBA-Induced Mammary Tumor Development",
abstract = "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 H 2O 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 H 2O 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 H 2O 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.",
author = "Yihong Kaufmann and Jacki Kornbluth and Zuliang Feng and Michael Fahr and Schaefer, {Robert F.} and Vicki Klimberg",
year = "2003",
month = "11",
language = "English (US)",
volume = "27",
pages = "411--418",
journal = "JPEN. Journal of parenteral and enteral nutrition",
issn = "0148-6071",
publisher = "SAGE Publications Inc.",
number = "6",

}

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, Vicki

PY - 2003/11

Y1 - 2003/11

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 H 2O 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 H 2O 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 H 2O 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 H 2O 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 H 2O 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 H 2O 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.

UR - http://www.scopus.com/inward/record.url?scp=1642513486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642513486&partnerID=8YFLogxK

M3 - Article

C2 - 14621122

AN - SCOPUS:1642513486

VL - 27

SP - 411

EP - 418

JO - JPEN. Journal of parenteral and enteral nutrition

JF - JPEN. Journal of parenteral and enteral nutrition

SN - 0148-6071

IS - 6

ER -