Volatile S-nitrosothiols and the typical smell of cancer

Abstract

An unconventional approach to investigations into the identification of typical volatile emissions during illnesses gives rise to the proposal of a new class of cancer markers. Until now, cancer markers seem not to have been conclusively identified, though the obvious behavior of dogs points to their existence. The focus has been directed towards molecules containing sulfurous functionalities. Among such compounds, S-nitrosothiols (SNOs) are known to be involved in important physiological processes in living organisms and they are described as being typically elevated in cancer. Volatile SNOs (vSNOs) are proposed to be the source of the significant smell of cancer. Synthetic vSNOs are known to have lifetimes of between some minutes and several hours, which may be the main reason as to why they have been ignored until now, and also for the inability of analytics to detect them in vivo. Based on typical structures occurring in the volatile sulfur organics being emitted from human breath, four vSNOs have been synthesized and characterized by tandem mass spectrometry and gas chromatography/mass spectrometry. Simulating the relatively fatty consistency of cancer tissue by diluting the samples in n-decane, surprisingly reduces their tendency to decompose to lifetimes of weeks even at room temperature. A sniffer dog was trained with the synthetic vSNOs, and the results of the tests indicate that synthetic and cancer smells are very similar or even the same. The findings can be a clue for further target-oriented systematic optimization of existing sensitive measurement methods to prove vSNOs as cancer emissions and finally establish future methods for cancer diagnosis based on screening for this new class of volatile illness markers.

Methanethiol: A Scent Mark of Dysregulated Sulfur Metabolism in Cancer

“…In a comparative analysis of volatiles in the exhaled breath of lung cancer patients employing solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) and subsequent canine detection, methanethiol-derived dimethyl disulfide was found to be the main compound responsible for discriminating between healthy individuals and cancer patients [80]. Moreover, volatile nitrosothiols that may result from the reaction of alkyl thiols with nitric oxide (NO) were reported to be recognized by a sniffer dog [81]. In this regard, the use of canine olfaction for non-invasive cancer diagnosis is also of high interest.…”

Unraveling the potential of breath and sweat VOC capture devices for human disease detection: a systematic-like review of canine olfaction and GC-MS analysis

“…Balancing the ability to trap both apolar and polar compounds is essential, as valuable information could be lost if the collection device favors only one type of compound. Preserving highly reactive compounds like thiol molecules before analysis would be a significant advancement in medical diagnosis applications involving body odors (Schroeder, 2015). 3.…”

Integrating exhaled breath diagnostics by disease-sniffing dogs with instrumental laboratory analysis

“…The ‘breath aerosol’ is comprised of small liquid particles enriched in the semi-volatiles, dissolved ionic material, bacteria, and larger organic compounds. Although much attention so far for cancer detection by breath analysis has been on the collection and analysis or on-line analysis of the volatiles (Filipiak et al 2014, Schroeder 2015, Gasparri et al 2016, Schallschmidt et al 2016), we believe that the semi-volatile constituents of the breath aerosol should be given more attention for two reasons. First, collection of the aerosols in breath can (via filtration, adsorption, or absorption) can be simpler than collecting the gas-phase with a focus on the volatiles.…”