Effect of phytochemical intervention on dibenzo[a,l]pyrene-induced DNA adduct formation

Abstract

Dibenzo[a,l]pyrene (DBP) has been found to be the most potent carcinogen of the polycyclic aromatic hydrocarbons (PAHs). Primary sources for DBP in the environment are combustion of wood and coal burning, gasoline and diesel exhaust, and tires. Given the likelihood of environmental exposure to DBP and strong experimental evidence of its potency, it is likely to contribute to lung cancer development. Intervention with compounds of natural origin (“phytochemicals”) is considered an effective means to prevent cancer development and favorably modulate the underlying mechanisms, including DNA adduct formation. In this study, several agents have been identified that inhibit environmental carcinogen-induced DNA adduct formation using a cell-free microsomal system. Of the ten agents tested, resveratrol (648 ± 26 adducts/109 nucleotides), oltipraz (1007 ± 348 adducts/109 nucleotides), delphinidin (1252 ± 142 adducts/109 nucleotides), tanshinone I (1981 ± 213 adducts/109 nucleotides), tanshinone IIA (2606 ± 478 adducts/109 nucleotides) and diindoylmethane (3643 ± 469 adducts/109 nucleotides) were the most effective compared to vehicle treatment (14,062 ± 1097 adducts/109 nucleotides). DBP is metabolized by phase I metabolizing enzymes CYP1A1, CYP1A2, and CYP1B1. DBP-induced DNA adducts can be inhibited by several mechanisms. We found that all the test agents inhibited DNA adducts by inhibiting one or more of these enzymes. Oltipraz inhibited DNA adducts entirely by inhibiting the CYP450s, while resveratrol and delphinidin inhibited DNA adducts by also interacting directly with the carcinogenic metabolite, anti-dibenzo(a,l)pyrene-11,12-dihydrodiol-13,14-epoxide.

Chemoprevention of Colorectal Cancer by Anthocyanidins and Mitigation of Metabolic Shifts Induced by Dysbiosis of the Gut Microbiome

“…Previous work from our laboratory against breast and lung cancer has shown that Anthos possess both chemopreventive and therapeutic effects due to their roles as anti-inflammatory, antioxidant agents and modulators of CYP1A1 and CYP1B1 (18). We demonstrated that intervention with the anthocyanidin, delphinidin favorably modulated the underlying mechanisms of potent PAHs (19). Furthermore, although work has been conducted to research the impact of anthocyanins on CRC (20,21), no data have been reported to study the impact of Anthos or ETBF bacteria on alterations in phase I and II enzyme expression.…”

A second polymorph of 3H-1,2-benzodithiole-3-thione

“…The title compound is a derivative of the 1,2-dithiole-3-thione family, which has attracted much interest because of the important bioactive properties and potential applications (Li et al, 2016, Russell et al, 2015, (Wallace et al, 2007). Recrystallization of 3H-1,2benzodithiole-3-thione in toluene solution leads to a monoclinic polymorph in the space group C2/c (Boukebbous et al, 2016) whereas recrystallization in diethyl ether solution leads to a second polymorph in the monoclinic system, and space group P2 1 /n (the present work).…”

Epigallocatechin Gallate and Caffeine Prevent DNA Adduct Formation and Interstrand Cross-Links Induced by Acrolein and Crotonaldehyde

“…A similar conclusion was drawn for polyphenols to intervene dibenzo[a,l]pyrene‐induced DNA adduct formation in a newly published paper (Russell et al . ). The inhibitory effects of EGCG against DNA adduct formation may explain why in a clinical trial that a diet rich of green tea polyphenols may reduce genotoxicity in the human urinary bladder of smokers (Talaska et al .…”