title: Gut glutathione metabolism and changes with 7,12-DMBA and glutamine.
abstract: BACKGROUND
  The mechanism by which oral glutamine (GLN) prevents 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN triples the negative extraction of gut glutathione (GSH) in rats, DMBA significantly disrupts it. Actual gut GSH flux has not been reported. We hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production and supplemental oral GLN antagonizes this effect.
  
  
  METHODS
  Eighty Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day) or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at 1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal blood was taken for GLN and GSH levels, and blood flow was measured using (14)C-PAH. Gut GLN and GSH fluxes (uptake or production) were calculated.
  
  
  RESULTS
  DMBA abrogated the normal GSH production (negative flux) in OIL + FA while not affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN.
  
  
  CONCLUSIONS
  Oral GLN restores to normal GSH production in DMBA-treated animals suggesting one of the mechanism(s) by which GLN prevents breast cancer in this model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block in GSH transport rather than actual intracellular production.
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Johnson
authors.forename: Yihong
authors.initials: Y
authors.lastname: Kaufmann
authors.forename: Shaoke
authors.initials: S
authors.lastname: Luo
authors.forename: Kirk
authors.initials: K
authors.lastname: Babb
authors.forename: Roger
authors.initials: R
authors.lastname: Hawk
authors.forename: V Suzanne
authors.initials: VS
authors.lastname: Klimberg
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000284:Administration, Oral; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis* / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002273:Carcinogens; D005973:Glutamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D005978:Glutathione