Effect of arsenic on benzo[a]pyrene DNA adduct levels in mouse skin and lung

Abstract

Concomitant exposures to arsenic and polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread. While BaP acts by binding to and inducing mutations in critical sites on DNA, the mechanism(s) of arsenic carcinogenesis remains unknown. Data from epidemiological studies of arsenic copper smelter workers and arsenic ingestion in drinking water suggest a positive interaction for arsenic exposure and smoking and lung cancer. A previous in vitro study showed that arsenic potentiated the formation of DNA adducts at low doses of BaP and arsenic. The present study was conducted to test the effect of arsenic on BaP-DNA adduct formation in vivo. We hypothesized that arsenic co-treatment would significantly increase BaP adduct levels in C57BL/6 mouse target organs: skin and lung. Treatment groups were: five mice, -BaP/-arsenic; five mice, -BaP/+arsenic; 15 mice, +BaP/-arsenic; 15 mice, +BaP/+arsenic. Mice in the appropriate groups were provided sodium arsenite in drinking water (2.1 mg/l), ad libitum, for 13 days (starting 9 days before BaP treatment), and 200 nmol BaP/25 ml acetone (or acetone alone) was applied topically, once per day for 4 days. DNA was extracted from skin and lung and assayed by (32)P-postlabeling. Statistical comparisons were made using independent t-tests (unequal variances assumed). BaP-DNA adduct levels in the +BaP groups were significantly higher than -BaP controls. Arsenic co-treatment increased average BaP adduct levels in both lung and skin; the increase was statistically significant in the lung (P = 0.038). BaP adduct levels in the skin of individual animals were positively related to skin arsenic concentrations. These results corroborate our in vitro findings and provide a tentative explanation for arsenic and PAH interactions in lung carcinogenesis.

Editor’s Highlight: Interactive Genotoxicity Induced by Environmentally Relevant Concentrations of Benzo(a)Pyrene Metabolites and Arsenite in Mouse Thymus Cells

“…There is also evidence showing that PARP contributes to XPA repair of double strand breaks (King et al, 2012). As þ3 has been documented to interact with other environmental agents, such as UVR (Cooper et al, 2009(Cooper et al, , 2013Evans et al, 2004;Zhou et al, 2011). There is also evidence showing that co-exposure with As þ3 increases BaP DNA adduct formation and mutations in mouse hepatoma Hepa-1 cells in vitro (Maier et al, 2002).…”

“…There is also evidence showing that co-exposure with As þ3 increases BaP DNA adduct formation and mutations in mouse hepatoma Hepa-1 cells in vitro (Maier et al, 2002). An in vivo study revealed that arsenic coexposure can increase BaP adducts formation in both lung and skin (Evans et al, 2004). However, studies have not addressed the effects of As þ3 and PAH co-exposure on immune cells in the thymus.…”

A no-carrier-added72Se/72As radionuclide generator based on solid phase extraction

“…The recent increasing interest in the element arsenic in environmental sciences [1], toxicology and carcinogenesis [2] and medicine [3,4] stimulates development of convenient and reproducible methods to trace this element and its compounds in subtoxic and subpharmaceutical concentrations. Arsenic has several isotopes of interest for medical or environmental application (cf.…”

Health risk assessment of mixed contaminants: Interaction of metals on the uptake of polycyclic aromatic hydrocarbons in human liver cells

“…It is noteworthy that the human health risk assessment of PAHs and metal/loids is carried out usually based on their individual toxicity. In published literature most studies have reported interaction of PAHs and metal/loids at binary combinations Lewińska et al, 2007;Evans et al, 2004;Mukherjee et al, 2004). However, in some recent publications the effects of PAHs and metal/loids interaction at ternary, quaternary 97 and up to seven compound mixtures on micronucleus formation (Cheng et al, 2015), Nrf2-antioxidant response pathway (Muthusamy et al, 2016b), oxidative stress (Muthusamy et al, 2016a) and cytotoxicity (Muthusamy et al, 2016c) following absorption and causing toxicity to liver cells Urani et al, 2005;Song et al, 2012;Babich et al, 1988).…”