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Genotoxicity of Thirdhand Smoke and Aged Secondhand Smoke

Institution: Lawrence Berkeley National Laboratory
Investigator(s): Bo Hang, Ph.D.; M.D.
Award Cycle: 2010 (Cycle 19) Grant #: 19XT-0070 Award: $427,204
Subject Area: General Biomedical Science
Award Type: Exploratory/Developmental Award

Initial Award Abstract
Today, approximately 2 billion smokers worldwide pose a constant threat of direct/indirect exposure to nearly 4 billion nonsmokers. Secondhand smoke (SHS) consists of several thousand individual chemicals produced mainly by the smoke from the burning tip of cigarettes between puffs (sidestream smoke, SSS) and the smoke exhaled by the smoker (mainstream smoke, MSS). Recently, exposure to thirdhand smoke (THS) - the aged SHS that is adsorbed onto surfaces, where it undergoes chemical transformation, and re-enters the indoor environment, has become a public health concern, because (1) it may become a long-term source of exposure to tobacco toxicants; and (2) it could be particularly harmful to toddlers as well as other occupational workers who may have close contact with contaminated surfaces. Previous studies from the cigarette industry showed that the aging of SSS leads to its increased toxicity. THS is expected to contain newly formed toxicants that may impose more severe and/or additional adverse effects on biological systems. However, little is known about the chemical composition and actual health effects of THS, especially the harm to structure and function of the genetic material, DNA, that can ultimately lead to diseases such as cancer.

SHS contains nicotine and many cancer-causing chemicals that are distributed between its vapor and particulate phases. We have found that during the aging of SHS, the less volatile organic chemicals, e.g., nicotine, nitrosamines and benzene-derivates, can be significantly adsorbed to indoor surfaces, and react with atmospheric species such as ozone, to yield new toxicants that remain on the indoor surfaces or enter the air, thus increasing health risks of exposure for nonsmokers. The aim of this proposal is to test in vitro the overall ability of THS and "aged" SSS/SHS to react with DNA, the most critical target for many tobacco carcinogens. We hypothesize that THS is a genotoxic chemical mixture capable of binding covalently to DNA (DNA adducts). In addition, we propose that the aging process of SSS/SHS leads to the formation of new types of DNA adducts, due to the reaction of their chemicals with environmental species that yields novel toxic byproducts.

Our groups at LBNL have been studying indoor and DNA adduct chemistry for certain major chemicals in SHS such as nicotine and benzene. Although THS is expected to be a complex chemical mixture, these two major groups of components present in SHS, i.e., nicotine and tobacco-specific nitrosamines (e.g., NNN and NNK), and benzene derivatives such as phenol and quinones, will be the main focus of this project. Chemicals of both groups include established carcinogens capable of forming DNA adducts and/or strand breaks, and some of them have affinity for surfaces due to their low volatility. In this project, SHS will be generated and reacted with ozone, using a chamber system developed at LBNL. SSS/SHS chemicals adsorbed onto cellulose (THS) and in aqueous condensates of aged SSS (SHS) will be tested for DNA damaging potential in two Aims: (1) To determine the overall ability of THS to produce adducts in DNA. We will use mass spectrometry and 32P-postlabeling to detect DNA adducts and the comet assay to measure DNA strand breaks. In addition, the possible changes in DNA adduct patterns during the SSS aging with ozone will be examined, which will be used to evaluate the formation of new toxicants and to seek a molecular explanation for the previously observed increased toxicity of aged SSS; and (2) To determine the identity of the major DNA adducts detected in Aim 1 using chromatographic and spectrometric methods. Structural analyses of characteristic DNA adducts with several tobacco smoke chemicals will also be performed to identify their parent compounds in smoke samples. Overall, our proposed work will be a critical step in a timely assessment of whether the THS exposure is genetically harmful to exposed nonsmokers, and the ensuing data will serve as the experimental evidence for framing and enforcing policies prohibiting smoking in homes, hotels, and cars in California and elsewhere in order to protect vulnerable people.

Thirdhand Tobacco Smoke: Emerging Evidence and Arguments for a Multidisciplinary Research Agenda
Periodical: Environmental Health Perspectives Index Medicus:
Authors: Matt GE, Quintana PJE, Destaillats H, Gundel LA, Mohamad S, Singer BC, Jacob III J, Benowi ART
Yr: Vol: Nbr: Abs: Pg:

Increased Risk of Lung Cancer Associated with a Functionally Impaired Polymorphic Variant of the Human DNA Glycosylase NEIL2
Periodical: DNA Repair Index Medicus:
Authors: Sanjib Dey, Amit K Maiti, Muralidhar L Hegde, Pavana M Hegde, Istvan Boldogh, Partha S Sar ART
Yr: 2012 Vol: Nbr: Abs: Pg: