Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 8;7(2):26.
doi: 10.3390/metabo7020026.

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

Stepan Melnyk  1   2 , Soheila Korourian  3 , Joseph W Levy  4   5 , Oleksandra Pavliv  6   7 , Teresa Evans  8   9 , Reza Hakkak  10   11   12
Affiliations

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

Stepan Melnyk et al. Metabolites. .

Abstract

The prevalence of the overweight and obesity is on the rise worldwide. Obesity can increase the risk of certain cancers and liver steatosis development. Previously, we reported that obesity increased liver steatosis in a mammary tumor model, but little is known about the effects of obesity in the liver in regard to global DNA methylation, DNA damage, and oxidative/nitrosative stress. Using a mammary tumor model, we investigated the effects of obesity on oxidative stress and DNA reaction. Five-week-old lean and obese female rats were used. At 50 days of age, all rats received 7,12-dimethylbenz(α)anthracene (DMBA) and were sacrificed 155 days later. HPLC with electrochemical and ultraviolet detection and LC-MS were used. Obesity caused higher (p < 0.0004) methionine levels, had no effect (p < 0.055) on SAM levels, caused lower (p < 0.0005) SAH levels, caused higher (p < 0.0005) SAM/SAH ratios, and increased (p < 0.02) global DNA methylation. Levels of free reduced GSH were not significantly lower (p < 0.08), but free oxidized GSSG was higher (p < 0.002) in obese rats. The GSH/GSSG ratio was lower (p < 0.0001), and oxidized guanosine was higher (p < 0.002) in DNA of obese rats compared to lean rats. Obesity caused significant oxidative/nitrosative stress, oxidative DNA damage, and change of DNA methylation pattern in the liver, and these changes may contribute to the development of liver steatosis in breast cancer models.

Keywords: DNA damage; liver; obesity; oxidative stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Methionine metabolism, DNA methylation, and DNA oxidative damage.
Figure 2
Figure 2
Left photomicrograph shows micro- and macro-vesicular steatosis in obese rats involving more than 75% of hepatocytes (original mag 40×, insert 100×). Right photomicrograph shows no evidence of fatty changes in lean rats (original mag 40×).
Figure 3
Figure 3
Multiple liner regression of SAM/SAH ratio and DNA methylation in liver of lean and obese Zucker rats.
Figure 4
Figure 4
Multiple liner regression of the GSH/GSSG ratio and DNA oxidation in liver of lean and obese Zucker rats.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ogden C.L., Carroll M.D., Kit B.K., Flegal K.M. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311:806–814. doi: 10.1001/jama.2014.732. - DOI - PMC - PubMed
    1. World Health Organization Obesity and Overweight. [(accessed on 1 March 2017)]; Available online: http://www.who.int/mediacentre/factsheets/fs311/en.
    1. Ng M., Fleming T., Robinson M., Thomson B., Graetz N., Margono C., Mullany E.C., Biryukov S., Abbafati C., Abera S.F., et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384 doi: 10.1016/S0140-6736(14)60460-8. - DOI - PMC - PubMed
    1. Mokdad A.H., Ford E.S., Bowman B.A., Dietz W.H., Vinicor F., Bales V.S., Marks J.S. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289:76–79. doi: 10.1001/jama.289.1.76. - DOI - PubMed
    1. Aleksandrova K., Stelmach-Mardas M., Schlesinger S. Obesity and liver cancer. Recent Results Cancer Res. 2016;208:177–198. - PubMed

LinkOut - more resources