Abstract
BACKGROUND: Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio ((15)N/(14)N), its recycling may cause cancer tissue to have lower (15)N/(14)N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their (15)N/(14)N. METHODS: Micro-biopsies of murine tumors and adjacent tissues were analyzed for (15)N/(14)N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. RESULTS: In the 7 mice analyzed, the brain tumors had distinctly lower (15)N/(14)N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the (15)N/(14)N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. CONCLUSIONS: The findings, coupled with the high sensitivity of the (15)N/(14)N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.