Can we use high precision metal isotope analysis to improve our understanding of cancer?

Abstract

High precision natural isotope analyses are widely used in geosciences to trace elemental transport pathways. The use of this analytical tool is increasing in nutritional and disease-related research. In recent months, a number of groups have shown the potential this technique has in providing new observations for various cancers when applied to trace metal metabolism. The deconvolution of isotopic signatures, however, relies on mathematical models and geochemical data, which are not representative of the system under investigation. In addition to relevant biochemical studies of protein-metal isotopic interactions, technological development both in terms of sample throughput and detection sensitivity of these elements is now needed to translate this novel approach into a mainstream analytical tool. Following this, essential background healthy population studies must be performed, alongside observational, cross-sectional disease-based studies. Only then can the sensitivity and specificity of isotopic analyses be tested alongside currently employed methods, and important questions such as the influence of cancer heterogeneity and disease stage on isotopic signatures be addressed.

Potential of non-traditional isotope studies for bioarchaeology

“…Non-traditional isotopes have recently been the subjects of many studies because of their potential to trace metabolic diseases such as hemochromatosis (Krayenbuehl et al 2005;Stenberg et al 2005, Walczyk and, iron deficiency (Van Heghe et al 2013), Wilson disease (Aramendía et al 2013;Resano et al 2013), cancers (Balter et al 2015;Larner et al 2015;Télouk et al 2015;Bondanese et al 2016;Chamel et al 2016) or bone mineral balance (Skulan et al 2007;Heuser and Eisenhauer 2010;Morgan et al 2011;Anbar et al 2013). The potential of these isotopes as a new diagnostic tool in biomedicine has recently been fully described in four reviews (Albarède et al 2016; δ 66 Zn (‰) Costas- Heuser 2016;Larner 2016). Even if it has not yet been investigated, mineralized tissues are likely to record isotopic signatures of these pathologies.…”

Stable isotope evidence (Fe, Cu) suggests that sex, but not aging is recorded in rhesus macaque (Macaca mulatta) bone

“…Fe and Cu are vital components in a multitude of biological processes related to oxygen transport, electron transport, and cellular respiration in organisms (Arredondo & Núñez, 2005; Albarède, 2015; Larner, 2016). Additionally, Fe and Cu are the main components of human serum and blood, which irrigates bone, therefore Fe is incorporated, and the isotopic compositions are recorded in bone (Balter et al, 2013;Jaouen et al, 2012; Jaouen et al, 2017).…”

Evidence of isotopic fractionation of natural uranium in cultured human cells

“…However, very little knowledge is available on the processes occurring at the molecular or cellular level that lead to the isotopic fractionation observed during metal transport in living organisms. Furthermore, the lack of investigation regarding isotopic fractionation in cellular models has recently been stressed (17). Such in vitro studies would be invaluable in understanding the processes at the origin of isotopic fractionation and to link these processes to cellular pathways of metals.…”