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Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats
Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
* Author to whom correspondence should be addressed.
Received: 2 May 2013; in revised form: 25 June 2013 / Accepted: 27 June 2013 / Published: 15 July 2013
Abstract: Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.
Keywords: hypertension; colon carcinogenesis; oxidative stress; inflammation; angiotensin-II
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Kochi, T.; Shimizu, M.; Ohno, T.; Baba, A.; Sumi, T.; Kubota, M.; Shirakami, Y.; Tsurumi, H.; Tanaka, T.; Moriwaki, H. Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats. Int. J. Mol. Sci. 2013, 14, 14700-14711.
Kochi T, Shimizu M, Ohno T, Baba A, Sumi T, Kubota M, Shirakami Y, Tsurumi H, Tanaka T, Moriwaki H. Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats. International Journal of Molecular Sciences. 2013; 14(7):14700-14711.
Kochi, Takahiro; Shimizu, Masahito; Ohno, Tomohiko; Baba, Atsushi; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka. 2013. "Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats." Int. J. Mol. Sci. 14, no. 7: 14700-14711.