Abstract
Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. Treatment of B[a]P induced cytotoxicity on HepG2 cells, whereas co-treatment of myricetin with B[a]P reduced the formation of the B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adduct, which recovered cell viability. Furthermore, we found a protective effect of myricetin against B[a]P-induced genotoxicity in rats, via myricetin-induced inhibition of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and BPDE-DNA adduct formation in the liver, kidney, colon, and stomach tissue. This inhibition was more prominent in the liver than in other tissues. Correspondingly, myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively. Taken together, this showed that myricetin attenuated B[a]P-induced genotoxicity via regulation of phase I and II enzymes. Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes.
Highlights
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental chemical carcinogens that lead to genetic damage and possess highly bioaccumulation characteristic [1]
Myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively
Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and Keywords: Benzo[a]pyrene; myricetin; oxidative stress; BPDE-DNA adduct; phase detoxifying enzyme
Summary
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental chemical carcinogens that lead to genetic damage and possess highly bioaccumulation characteristic [1]. Benzo[a]pyrene (B[a]P) is a well-known PAH (Figure 1A), which is listed as group 1 carcinogens by the International. This means that humans are exposed to a low dose of B[a]P over a lifetime. The long-term exposure of B[a]P can cause angiogenesis and metastasis in the skin, lungs, liver, colorectal and stomach [4]. Other studies support that long-term exposure of low-dose B[a]P induces cell angiogenesis and metastasis [5], and a low dose of B[a]P toxicity is enhanced by interaction with
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