Timing of oral glutamine on DMBA-induced tumorigenesis

Introduction. A single dose of oral 7,12-dimethylbenz(a)anthracene (DMBA) in pubertal rats causes breast tumors by 11 weeks and is associated with ablation of the normal gut glutathione (GSH) production for up to 4 weeks. We hypothesized that glutamine (GLN), known to restore the gut GSH production inhibited by DMBA, given only during this 4-week period, would prevent breast cancer initiation. Methods. 160 Female Sprague-Dawley rats were divided to 10 groups (n = 16/group): Long Term (LT): DMBA + GLN, DMBA + FA, DMBA + H2O, OIL + GLN, OIL + FA, OIL + H2O; Short Term (ST): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA At age 50 days old, rats received a one-time dose of 100 mg/kg DMBA or sesame oil. LT rats were gavaged daily with isonitrogenous GLN, (FA), or water (H2O) the entire study. ST rats were gavaged with GLN, freamine, or H2O the first 4 weeks and then H2O the remaining 7 weeks. All rats were pair-fed defined chow. Rats were sacrificed at 11 weeks, observed for tumors, blood assayed for GLN, GSH, gut GLN and GSH and uptake or production calculated using labeled C-14-PAH. Results. ST and LT GLN were equally effective in preventing tumor formation. GLN doubled gut GSH production in LT animals as compared to all other groups (P < 0.05). Control rats developed no tumors and had superior gut GSH production as compared with tumor-bearing rats. Conclusions. Oral GLN when given only during the 4 weeks of known gut GSH ablation had the same tumor prevention efficacy as prolonged GLN administration. Not previously reported, GLN appears to affect the initiation of tumor formation in this model.