Fig. 6

Illustration of the impacts of different ratios of metabolic N efflux and growth on tissue δ¹⁵N, as an explanation for the lower δ¹⁵N of tumor tissue. δ¹⁵N_in is the δ¹⁵N of external N supply to the organ in question. ε is a measure of the amplitude of the isotope effect of ammonium catabolism and efflux. Here, a higher ε denotes a stronger preference for ¹⁴N relative to ¹⁵N in the conversion (see text). Δδ¹⁵N(cancer-healthy) refers to the δ¹⁵N difference between tumor tissue and healthy equivalent. Box colors are as follows: green: healthy tissue with high metabolism (100% of N input is effluxed as ammonium); yellow: healthy tissue with low metabolism (or more precisely, low metabolism-to-growth ratio, with 50% of N input effluxed as ammonium); red: tumor tissue with high growth and no ammonium efflux. In (a), healthy and tumor tissues are considered as isolated. In (b), as part of its N supply, tumor tissue also taps extracellular ammonium effluxed from healthy tissue. Tops of both (a) and (b): high metabolism mode (qualitatively corresponding to neural tissue in our experiments). Bottoms of (a) and (b): low metabolism mode (corresponding to head&neck tissue)