Partial role of volatile organic compounds in behavioural responses of mice to bedding from cancer-affected congeners

Abstract

Tumours induce changes in body odours. We compared volatile organic compounds (VOCs) in soiled bedding of a lung adenocarcinoma male mouse model in which cancer had (CC) versus had not (NC) been induced by doxycycline at three conditions: before (T0), after 2 weeks (T2; early tumour development), after 12 weeks (T12; late tumour development) of the induction. In an earlier study, wild-derived mice behaviourally discriminated between CC and NC soiled bedding at T2 and T12. Here, we sought to identify VOCs present in the same soiled bedding that could have triggered the behavioural discrimination. Solid phase micro-extraction was performed to extract VOCs from 3 g-sample stimuli. While wild-derived mice could discriminate the odour of cancerous mice at a very early stage of tumour development (T2), the present study did not identify VOCs that could explain this behaviour. However, consistent with the earlier behavioural study, four VOCs, including two well-known male mouse sex pheromones, were found to be present in significantly different proportions in soiled bedding of CC as compared to NC at T12. We discuss the potential involvement of non-volatile molecules such as proteins and peptides in behavioural discrimination of early tumour development (T2), and point-out VOCs that could help diagnose cancer.

Keywords: Mus musculus; Cancer biomarkers; EGFR cancer; Inter-SPME-fibre reliability; Odour signature; SPME; Soiled bedding.

Fig. 1.

Redundancy analysis (RDA) plots picturing, in the left panel, the outcome of model 3 (Table 2) testing the effect of health status (NC/CC) and experimental conditions (T0-T12) on variation of VOCs levels. The correlation circle indicates compounds showing an absolute correlation coefficient >0.8 with the two main axes of the RDA.

Fig. 2.

Schematic representation of the experimental protocol. Each bag contained pooled soiled bedding from three to four different mice. These pools of soiled bedding were also used as stimuli in the earlier behavioural study (Gouzerh et al., 2022a). Soiled bedding was sampled at different times (experimental conditions): T0: before treatment; T2: after 2 weeks of doxycycline treatment; T12: after 12 weeks of doxycycline treatment. The adsorbent phase of the SPME fibre was exposed for 1 h to a given soiled bedding sample.