Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice

Abstract

Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups b a s e d o n t h e i r e x p o s u r e t o C U S a l o n e , 7 , 1 2 -dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage.

Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

“…Earlier studies from our laboratory have shown that CUS enhanced both the nephrotoxic and hepatotoxic potential of 7,12-dimethylbenz(a) anthracene in Swiss albino mice ( Suhail et al, 2011 ), by altering the oxidative stress and compromising the antioxidant system, thus stress may act as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Moreover, CUS also aggravated the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice which further strongly supported our studies on the effect of stress on cancer promotion through DNA damage and modulation of oxidant/antioxidant system in vivo ( Suhail et al, 2015 ). Thus, irrespective of the carcinogen used or the mode of application topical ( Suhail et al, 2011 , 2015 ) or oral as in the present study, CUS increased the toxic potential of the carcinogens.…”

“…One enzyme unit is defined as the amount of enzyme (Suhail et al, 2015) decomposing 1 μM H 2 O 2 per minute at 25°C.…”

“…The CAT activity was measured in 0.05 M phosphate buffer (pH 7.0) by following the decrease in absorbance at 240 nm due to decomposition of 30 mM hydrogen peroxide ( Aebi, 1984 ; Zafir and Banu, 2009 ). One enzyme unit is defined as the amount of enzyme ( Suhail et al, 2015 ) decomposing 1 μM H 2 O 2 per minute at 25°C.…”

Effects of oral administration of various essential oils on blood metabolites, intestine development, microbial enumeration and meat quality in broilers

“…The Yellowness(b)* values of the muscles of the THY and ORE groups were significantly reduced by 27.46% (P<0.05) and 24.38(P<0.05) compared to the control group (13.00). It might be that the essential oils have a function of antioxidant in laboratory studies (Suhail et al, 2015;Bi et al, 2016). It is reported that that the active ingredients of essential oils from Anoectochilus roxburghii can eliminate free radicals including 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitropheny l) hydrazyl (DPPH); 2, 2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and the superoxide anion (O2-) (Shao et al, 2014).…”

Chronic Unpredictable Mild Stress Accelerates the Growth of Bladder Cancer in a Xenograft Mouse Model

“…Mice were randomly divided into CUMS (n=10) or control (n=10) groups after the in vivo implantation of tumor cells. The CUMS procedure was conducted as previously described [11][12][13] but adjusted slightly. Briefly, stress regimes were administered, consisting of the following eight stressors: food deprivation (24 h), water deprivation (24 h), tail pinch (5 min, 1 cm from the distal portion of the tail), cold swimming (3 min at 4°C), physical restraint (2 h), moist bedding (6 h), 30° cage tilt (12 h) and overnight stroboscopic lighting.…”