LATE-BREAKING ABSTRACT: Effects of long term intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) on spontaneous tumorigenesis in aged mice

Autor: Sara Yubero, Elvira Gonzalez-Obeso, Ramon Farré, Teresa Gallego-Martin, Elena Olea, Ana Obeso, Constancio Gonzalez
Rok vydání: 2015
Předmět:
Zdroj: 4.2 Sleep and Control of Breathing.
Popis: Background: Recent studies have reported, albeit with discrepancies, an association between severity of OSA and cancer incidence/mortality. Discrepancies are likely due to the large number of OSA-linked comorbidities and uncontrolled variables among patients.In mice, short term IH mimicking OSA augments tumour growth and metastasis of implanted tumours, but whether or not IH enhances spontaneous tumorigenesis has not been studied. Aim: To test the hypothesis that long term IH increases spontaneous tumorigenesis in mice. Methods: The study was designed with IH as the only variable. To mimic the situation in humans in terms of genetic diversity, outbreed mice (Swiss CD1) were used. IH was long-lasting (8/h day; 3 months; ∼8-10 yr at human scale) and was applied from age 15 to 18 months, equivalent to a human age (50-60 yr) with high tumorigenesis and OSA rates. Two intensities of IH were used: 80 s air/40 s 12% O 2 (N=49) or 7.5% O 2 (N=53). Control mice (N=55) remained in room air. On sacrifice, blood and tissues were collected to determine tumoral markers. Necropsy allowed macroscopic identification of tumoral masses which were stored (4% formaldehyde) for histology. Results: Tumoral masses were found in 36.4% of control mice (8 liver, 7 lung, 5 skin), in 38.8% of 12% O 2 IH mice (11 liver, 7 lung, 1 skin) and in 63.5% (χ 2 = 7.85; p= 0.005 vs. control) of the 7.5% O 2 IH mice (11 liver, 15 lung, 7 skin). Conclusion: IH mimicking OSA augments multi-organ spontaneous tumorigenesis in a O 2 desaturation-related manner. Data would help to interpret cancer incidence in OSA patients. Support: Spanish Association Against Cancer (AECC) and CIBERES, ISCiii, Spain.
Databáze: OpenAIRE