Abstract
Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the 32P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids.
Highlights
Introduction iationsA total of 1,898,160 (254,170 for lung and bronchus) new cancer cases and 608,570(137,040 for lung and bronchus) cancer deaths were predicted to occur in the U.S in 2021 [1].Human and animal data have shown that environmental factors (e.g., polycyclic aromatic hydrocarbons (PAHs)) from cigarette smoke, air and water pollution contribute to the etiology of cancers [2,3]
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major omega-3 fatty acids in fish oil (FO). These results suggested that omega3 fatty acids including EPA and DHA may play key roles in FO-mediated attenuation of PAH-DNA adduct levels
Our results suggest that EPA and DHA may play a role as nutritional inhibitors of CYP1B1
Summary
Introduction iationsA total of 1,898,160 (254,170 for lung and bronchus) new cancer cases and 608,570(137,040 for lung and bronchus) cancer deaths were predicted to occur in the U.S in 2021 [1].Human and animal data have shown that environmental factors (e.g., polycyclic aromatic hydrocarbons (PAHs)) from cigarette smoke, air and water pollution contribute to the etiology of cancers [2,3]. A total of 1,898,160 (254,170 for lung and bronchus) new cancer cases and 608,570. (137,040 for lung and bronchus) cancer deaths were predicted to occur in the U.S in 2021 [1]. Human and animal data have shown that environmental factors (e.g., polycyclic aromatic hydrocarbons (PAHs)) from cigarette smoke, air and water pollution contribute to the etiology of cancers [2,3]. People living near Superfund sites are exposed to PAHs [4]. PAHs are ranked to be 9th in the national priority list of toxic substances. Benzo(a)pyrene (BP) and benzo(b)fluoranthene (BbF) are ranked high (8th and 10th), on this list, and are considered to be contaminants of concern (COC) at Superfund sites. PAHs by themselves are inert, but exhibit their cellular effects through metabolism by cytochrome
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