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

Abstract

Background Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N 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 15N/14N. Methods Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N 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 15N/14N 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 15N/14N 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 15N/14N 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.

Laboratory Assessment of the Impact of Chemical Oxidation, Mineral Dissolution, and Heating on the Nitrogen Isotopic Composition of Fossil‐Bound Organic Matter

“…The stable isotopes of nitrogen ( 14 N and 15 N) can offer important insights into present and past changes in the cycling of this key element through organisms, food webs, and environments (Casciotti, 2016; Deniro & Epstein, 1981; Fripiat et al., 2021; Sigman & Fripiat, 2019; Straub et al., 2021; Wolf et al., 2009). Their use in paleo‐reconstructions requires the development of faithful geochemical archives that are unaffected by diagenetic alteration and/or contamination by exogenous N. In recent years, the analysis of the N isotopic composition of the organic matter bound within the mineral structure of fossil skeletons (e.g., foraminifera, corals, diatoms, otoliths, and tooth enamel) has emerged as a promising archive of the original isotopic signature of the organism that is protected from degradation for thousands to millions of years (Ai et al., 2020; Altabet & Curry, 1989; Duprey et al., 2020; Erler et al., 2016, 2020; Farmer et al., 2021; Kast et al., 2019, 2022; Leichliter et al., 2021; Lueders‐Dumont et al., 2018; Martinez‐Garcia et al., 2014; Ren et al., 2009, 2017; Robinson et al., 2004, 2005; Shemesh et al., 1993; Sigman et al., 1999, 2021; Straub et al., 2013; Studer et al., 2015, 2018, 2021; Wang et al., 2014, 2016, 2017).…”

Oral Cavity Cancer Tissues Differ in Isotopic Composition Depending on Location and Staging

“…Recent findings support the diagnostic use of nitrogen isotopic analysis in the differentiation of malignant from healthy tissues. The novel analytical method proposed by Straub M. et al allows for the assessment of the amount of tumour cell infiltration at the tumour margin, which is one of the most significant problems following surgery, as it is related to tumour recurrence [ 30 ].…”