The Radicals in Cigarette Tar: Their Nature and Suggested Physiological Implications

Pryor, William A.; Hales, Brian J.; Premović, Pavle; Church, Daniel F.

doi:10.1126/science.6301009

Cited by 276 publications

(191 citation statements)

References 14 publications

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“…Cigarette smoking, with its .4000 compounds and 10 14 free radicals per puff, represents a major environmental stress (26)(27)(28)(29). Consistent with our observations in the SAE, several studies have demonstrated that cigarette smoke in vivo and in vitro can mediate differences in the methylation status of individual genes in lung cells as well as non-lung cells.…”

Section: Smoking-associated Changes In Lung Dna Methylationsupporting

confidence: 76%

“…With this background, we hypothesized that cigarette smoke, with its .4000 compounds and 10 14 oxidants per puff, may have profound effects on the methylome of the small airway epithelium (SAE), the cell population that takes the initial stress of cigarette smoke and is the first site of lung pathology in cigarette smokers (26)(27)(28)(29)(30)(31)(32). In humans, the SAE consists of four major cell types: ciliated, secretory, columnar and basal cells (30,33).…”

Section: Introductionmentioning

confidence: 99%

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Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

Buro-Auriemma

Salit

Hackett

et al. 2013

Human Molecular Genetics

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The small airway epithelium (SAE), the first site of smoking-induced lung pathology, exhibits genome-wide changes in gene expression in response to cigarette smoking. Based on the increasing evidence that the epigenome can respond to external stimuli in a rapid manner, we assessed the SAE of smokers for genome-wide DNA methylation changes compared with nonsmokers, and whether changes in SAE DNA methylation were linked to the transcriptional output of these cells. Using genome-wide methylation analysis of SAE DNA of nonsmokers and smokers, the data identified 204 unique genes differentially methylated in SAE DNA of smokers compared with nonsmokers, with 67% of the regions with differential methylation occurring within 2 kb of the transcriptional start site. Among the genes with differential methylation were those related to metabolism, transcription, signal transduction and transport. For the differentially methylated genes, 35 exhibited a correlation with gene expression, 54% with an inverse correlation of DNA methylation with gene expression and 46% a direct correlation. These observations provide evidence that cigarette smoking alters the DNA methylation patterning of the SAE and that, for some genes, these changes are associated with the smoking-related changes in gene expression.

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Section: Smoking-associated Changes In Lung Dna Methylationsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

Buro-Auriemma

Salit

Hackett

et al. 2013

Human Molecular Genetics

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“…7 It is postulated that smoking affects the pathogenesis of AMD by a variety of methods including promoting oxidative damage, inducing angiogenesis, impairing the choroidal circulation, and by activating the immune system including complement pathway. [8][9][10][11][12][13] Stopping smoking reduces the risk of AMD and after 20 years of cessation the risk of developing AMD is the same as for non-smokers. 14 In the last few years, the genetic factors significantly contributing to AMD risk have been identified.…”

Section: Introductionmentioning

confidence: 99%

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Rennie

Stinge

King

et al. 2011

Eye

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Aims Smoking can increase the risk of macular degeneration and this is more than additive if a person also has a genetic risk. The purpose of this study was to examine whether knowledge of genetic risk for age-related macular degeneration (AMD) could influence motivation to quit smoking. Methods A questionnaire-based study of hypothetical case scenarios given to 49 smokers without AMD. Participants were randomly allocated to a generic risk, high genetic risk, or low genetic risk of developing AMD scenario. Results Forty-seven percent knew of the link between smoking and eye disease. In all, 76%, 67%, and 46% for the high risk, generic, and low risk groups, respectively, would rethink quitting (P for trend ¼ 0.082). In all, 67%, 40%, and 38.5%, respectively, would be likely, very likely, or would definitely quit in the following month (P for trend ¼ 0.023). Few participants (o16% of any group) were very likely to or would definitely attend a quit smoking session with no difference across groups. In all, 75.5% of participants would consider taking a genetic test for AMD. Conclusion In this pilot study, a trend was seen for the group given high genetic risk information to be more likely to quit than the generic or low genetic risk groups. Participants were willing to take a genetic test but further work is needed to address the cost benefits of routine genetic testing for risk of AMD. More generic risk information should be given to the public, and health warnings on cigarette packets that 'smoking causes blindness' is a good way to achieve this.

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“…The protective action of P-carotene may be explained by its anti-oxidant capacity to quench highly reactive singlet oxygen and free radical species (Krinsky, 1989). Free radicals are abundant in cigarette smoke and tar (Pryor et al, 1983) and are believed to initiate cancer by damaging DNA (Pryor, 1987). In addition, P-carotene has been hypothesised to be effective after conversion to retinol at a tissue or cellular level (de Vet, 1989).…”

Section: Discussionmentioning

confidence: 99%

Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum

Poppel

Kok²,

Hermus³

1992

Br J Cancer

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Summary P-carotene has been hypothesised to reduce lung cancer risk. We studied the effect of 14 weeks of P-carotene supplementation (20 mg d-1) on the frequency of micronuclei in sputum in 114 heavy smokers in a double-blind trial. Micronuclei reflect DNA damage in exfoliated cells and may thus provide a marker of early-stage carcinogenesis.Pre-treatment blood levels of cotinine, P-carotene, retinol and vitamins C and E were similar in the placebo group (n = 61) and the treatment group (n = 53). Plasma 1-carotene levels increased 13-fold in the treatment group during intervention. Initial micronuclei counts (per 3,000 cells) were higher in the treatment group than in the placebo group (5.0 vs 4.0, P<0.05). During intervention, the treatment group showed a 47% decrease, whereas the placebo group showed a non-significant decrease (16%). After adjustment for the initial levels, the treatment group had 27% lower micronuclei counts than the placebo group at the end of the trial (95% CI: 9-41%).These results indicate that P-carotene may reduce lung cancer risk in man by preventing DNA damage in early-stage carcinogenesis.The scientific interest in the role of carotenoids and retinoids in the prevention of human cancer has culminated in recent years (Editorial, 1991;Meyskens, 1990 al., 1987;Fontham, 1990). Since these studies cannot prove causal associations, two large randomised trials are currently conducted to evaluate the beneficial effect of P-carotene on human cancer development (Hennekens & Eberlein, 1985;Albanes et al., 1986). These intervention studies, however, provide little information on biological mechanisms.Damage to DNA is considered a crucial mechanism in cancer development (Weinstein, 1988). Micronuclei, DNA fragments in exfoliated cells, may thus provide a marker of early-stage carcinogenesis in target tissues (Lippman et al., 1990a,b;Stich et al., 1984a). In cigarette smokers, elevated micronuclei counts in expectorated sputum (Fontham et al., 1986) or bronchial brushings (Lippman et al., 1990a) are thought to reflect increased lung cancer risk.So far, no studies have investigated the effect of P-carotene supplementation on sputum micronuclei, as a reflection of lung cancer risk. P-Carotene has been shown to reduce micronucleated buccal mucosal cells in tobacco chewers (Stich et al., 1984a(Stich et al., , 1985(Stich et al., , 1988 and may thus reduce risk for oral cancer. These trials, however, did not measure plasma levels of P-carotene and retinol. Moreover, other antioxidant vitamins may modify the effects of P-carotene (Meyskens, 1990 Blood and sputum samples were collected before and after the 14-week treatment. The participants were instructed to take capsules daily with the evening meal, two capsules per day during the first 2 weeks, followed by one capsule per day over the next 12 weeks. Every 4 weeks, the participants were sent their next strip of 28 capsules, and were asked to return the used strips with the capsules not taken to monitor compliance. In addition, P-carotene was determined...

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The Radicals in Cigarette Tar: Their Nature and Suggested Physiological Implications

Cited by 276 publications

References 14 publications

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum

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