PhD Scientific Days 2023

Pathology - Posters C

Morphological Characteristics of Colon Adenocarcinoma in Male Mice with Different Resistance to Hypoxia

Text of the abstract

Introduction
In the mechanisms of colon cancer, one of the key factors is oxygen deficiency. Organisms differ in resistance to hypoxia. Probably, individual resistance to hypoxia can determine the severity of tumor process.
Aims
To characterize the morphological features of colon tumors in male C57Bl/6 mice with different resistance to hypoxia.
Method
Hypoxia resistance was assessed through physiological response to oxygen deprivation using decompression chamber test. The animals were exposed, one at a time, to simulated hypobaric hypoxia equivalent to 10,000 m altitude using a mercury barometer-coupled decompression chamber. Time length till the first sign of characteristic hyperventilatory response (‘gasping time’) was recorded using an electronic stopwatch. Based on gasping time, the animals were assigned to three groups: ‘susceptible’ (<3 min s, n=20), ‘normal’ (3–9 min, n=17) and ‘tolerant’ (>9 min, n=23). The ‘normal’ group was excluded from subsequent experiments. All mice survived the decompression chamber test and resumed their normal activity without signs of trauma.
The AOM/DSS (azoxymethane/dextran sodium sulfate) model was used to induce colon tumors. This model consisted of a single injection of AOM and two 1% DSS cycles for 7 days and 0.5% for 5 days. Animals were taken out of the experiment on the 71st day after AOM injection. On histological sections, the area of tumors and their malignancy were assessed, the composition of immune cells was analyzed using flow cytometry, and a blood analysis was performed. The nonparametric Mann-Whitney U test was used to assess the statistical significance of differences.
Results
Mortality was observed in both experimental groups (3 tolerant mice and 2 susceptible mice died). The development of tumors was more often in tolerant to hypoxia mice compared to susceptible (76.19% and 69.23%, respectively). The area of tumors did not differ significantly in animals with different resistance to hypoxia (p-value = 0.34). The relative number of monocytes in the blood increased only in tolerant to hypoxia mice during the development of tumors. Metastasis of tumors to the lymph nodes, liver and lungs was not detected.
Conclusion
Thus, on the 71st day after AOM injection, no statistically significant differences in the incidence and size of tumors were found in tolerant and susceptible to hypoxia animals.
Funding
This work was supported by Russian Science Foundation grant number 23-25-00294 “Individual tolerance to hypoxia and molecular-biological features of tumor growth initiation in an experimental model of colorectal cancer”.