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Intermittent hypoxia promotes carcinogenesis in azoxymethane and dextran sodium sulfate‐induced colon cancer model
Author(s) -
Yoon Dae Wui,
Kim YiSook,
Hwang Soyoung,
Khalmuratova Roza,
Lee Mingyu,
Kim Jee Hyun,
Lee Gah Young,
Koh SeongJoon,
Park JongWan,
Shin HyunWoo
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22957
Subject(s) - azoxymethane , oxidative stress , carcinogenesis , intermittent hypoxia , colorectal cancer , reactive oxygen species , hypoxia (environmental) , cancer , biology , endocrinology , deoxyguanosine , cancer research , medicine , pharmacology , chemistry , obstructive sleep apnea , biochemistry , oxygen , organic chemistry
Intermittent hypoxia (IH), a characteristic of obstructive sleep apnea, is known to promote cancer progression and aggressiveness in mouse models. However, little is known regarding the effect of IH on cancer initiation. Here, the effect of IH on carcinogenesis was explored in azoxymethane (AOM) and dextran sodium sulfate (DSS)‐induced colon cancer models with three different protocols. In the first protocol, two other application time points (early or late initiation of IH) were applied. In the second protocol, mice were divided into only two groups, and then exposed to either N or IH conditions for 14 days. In the third protocol, a pharmacological inhibition study for anti‐inflammation (5‐aminosalicylate) or anti‐oxidative stress (N‐acetylcysteine [NAC]) was performed. The number of tumors was significantly higher in the IH‐1 than in the N or IH‐2 groups. 8‐oxo‐2′‐deoxyguanosine (8‐OHdG) levels were higher in tumors of the IH‐1 group than in that of the N and IH‐2 groups. Gene expression related to reactive oxygen species production was higher in the IH‐1 group than in the N and IH‐2 groups, and it showed a positive correlation with 8‐OHdG levels. Prior to cancer development 8‐OHdG levels were already elevated in colonic epithelial regions in the IH group, possibly due to an imbalance between oxidative stress and antioxidant systems. NAC treatment resulted in a significant reduction in the number of tumors in mice exposed to IH. In conclusion, IH promotes carcinogenesis in a chemically‐induced colon cancer model where elevated 8‐OHdG may contribute to the increased tumor induction.