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. 2019 Apr;19(2):178-190.
doi: 10.1007/s12012-018-9488-5.

Effects of Ambient Atmospheric PM2.5, 1-Nitropyrene and 9-Nitroanthracene on DNA Damage and Oxidative Stress in Hearts of Rats

Lifang Zhao  1 , Li Zhang  1 , Minghui Chen  1 , Chuan Dong  1 , Ruijin Li  2 , Zongwei Cai  3
Affiliations

Effects of Ambient Atmospheric PM2.5, 1-Nitropyrene and 9-Nitroanthracene on DNA Damage and Oxidative Stress in Hearts of Rats

Lifang Zhao et al. Cardiovasc Toxicol. 2019 Apr.

Abstract

Exposure to fine particulate matter (PM2.5) increased the risks of cardiovascular diseases. PM2.5-bound 1-nitropyrene (1-NP) and 9-nitroanthracene (9-NA) are released from the incomplete combustion of fossil fuels and derived from polycyclic aromatic hydrocarbons (PAHs). The toxicities of 1-NP and 9-NA are mainly reflected in their carcinogenicity and mutagenicity. However, studies of PM2.5-bound 1-NP and 9-NA on the cardiac genotoxicity are limited so far. In this study, histopathology, DNA damage, DNA repair-related gene expression, and oxidative stress were investigated in the hearts of male Wistar rats exposed to PM2.5 [1.5 mg/kg body weight (b.w.)] or three different dosages of 1-NP (1.0 × 10- 5, 4.0 × 10- 5, and 1.6 × 10- 4 mg/kg b.w.) or 9-NA (1.3 × 10- 5, 4.0 × 10- 5, and 1.2 × 10- 4 mg/kg b.w.). The results revealed that (1) PM2.5, higher dosages of 1-NP (4.0 × 10- 5 and 1.6 × 10- 4 mg/kg b.w.) and 9-NA (4.0 × 10- 5 and 1.2 × 10- 4 mg/kg b.w.) caused obvious pathological responses and DNA damage (DNA strand breaks, 8-OHdG formation and DNA-protein cross-link), accompanied by increasing OGG1 and GADD153 expression while inhibiting MTH1 and XRCC1 expression in rat hearts. Also, they elevated the hemeoxygenase-1 (HO-1), glutathione S-transferase (GST), and malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) activity compared with the control. (2) The lowest dosages 1-NP or 9-NA could not cause DNA damage and oxidative stress. (3) At the approximately equivalent dose level, PM2.5-induced DNA damage effects were more obvious than 1-NP or 9-NA along with positive correlation. Taken together, heart DNA damage caused by PM2.5, 1-NP and 9-NA may be mediated partially through influencing the DNA repair capacity and causing oxidative stress, and such negative effects might be related to the genotoxicity PM2.5, 1-NP, and 9-NA.

Keywords: 1-Nitropyrene; 9-Nitroanthracene; DNA damage; Fine particulate matter; Oxidative stress; Rat heart.

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