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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.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12885-021-08489-x.

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies