Fate and Effects of Acrolein

Ghilarducci, David; Tjeerdema, Ronald S.

doi:10.1007/978-1-4612-2550-8_2

Cited by 192 publications

(215 citation statements)

References 137 publications

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“…It has been found that Acr is one of the most effective agents to deplete glutathione (1,5,6). We found that the NHBE are significantly more resistant than A549 cells and NHLF toward Acr-induced inhibition of NER and BER capacity.…”

Section: Discussionmentioning

confidence: 62%

“…Consequently, in Acr-exposed cells, many more Acr have already reacted with cellular proteins, including repair proteins, when Acr reacts with genomic DNA forming Acr-dG adducts. Because Acr modifications can cause protein dysfunction (1,5,6), this scenario may account for the lack of Acr-dG adduct repair in Acrtreated cells.…”

Section: Discussionmentioning

confidence: 99%

“…Acr is a major metabolite of antitumor drugs cyclophosphamide and ifosfamide. Metabolically produced and inhaled Acr are excreted in urine and accumulated in the bladder (5,6). It has been concluded that Acr is the culprit of bladder cancer in patients who have been administered cyclophosphamide and ifosfamide in long term treatment protocols (4 -7).…”

mentioning

confidence: 99%

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Effect of Carcinogenic Acrolein on DNA Repair and Mutagenic Susceptibility

Wang

Tong

et al. 2012

Journal of Biological Chemistry

148

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Background: Acrolein is highly reactive and abundant in tobacco smoke. Results: Acrolein induces DNA damage, inhibits excision repair and mismatch repair, causes repair protein degradation, and enhances mutagenesis. Conclusion: Acrolein induces DNA damage and inhibits DNA repair that causes mutagenesis and initiates carcinogenesis. Significance: This is the first demonstration that acrolein inhibits DNA repair pathways by induction of repair protein degradation.Acrolein (Acr), a ubiquitous environmental contaminant, is a human carcinogen. Acr can react with DNA to form mutagenic ␣-and ␥-hydroxy-1, N 2 -cyclic propano-2-deoxyguanosine adducts (␣-OH-Acr-dG and ␥-OH-Acr-dG). We demonstrate here that Acr-dG adducts can be efficiently repaired by the nucleotide excision repair (NER) pathway in normal human bronchial epithelia (NHBE) and lung fibroblasts (NHLF). However, the same adducts were poorly processed in cell lysates isolated from Acr-treated NHBE and NHLF, suggesting that Acr inhibits NER. In addition, we show that Acr treatment also inhibits base excision repair and mismatch repair. Although Acr does not change the expression of XPA, XPC, hOGG1, PMS2 or MLH1 genes, it causes a reduction of XPA, XPC, hOGG1, PMS2, and MLH1 proteins; this effect, however, can be neutralized by the proteasome inhibitor MG132. Acr treatment further enhances both bulky and oxidative DNA damage-induced mutagenesis. These results indicate that Acr not only damages DNA but can also modify DNA repair proteins and further causes degradation of these modified repair proteins. We propose that these two detrimental effects contribute to Acr mutagenicity and carcinogenicity.Acrolein, an ␣,␤-unsaturated aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes (1). Acr 2 is also a by-product of lipid peroxidation generated endogenously in cells under oxidative stress (2). Inhaled Acr is extremely toxic in mouse models (3). In fact, the effects of Acr on lung carcinogenicity in mouse models have not been assessed due to excessive death of Acr-exposed mice (3). Nonetheless, it has been shown that intraperitoneal injection of Acr causes bladder tumors in rat models (4 -7). Acr is a major metabolite of antitumor drugs cyclophosphamide and ifosfamide. Metabolically produced and inhaled Acr are excreted in urine and accumulated in the bladder (5, 6). It has been concluded that Acr is the culprit of bladder cancer in patients who have been administered cyclophosphamide and ifosfamide in long term treatment protocols (4 -7).Acr induces ␣-and ␥-hydroxy-1,N 2 -cyclic propano-2Ј-deoxyguanosine (␣-OH-Acr-dG and ␥-OH-Acr-dG) adducts in human cells (8). It has been found that both types of Acr-dG adducts are mutagenic and that they induce mainly G to T and G to A mutations (9 -18). By mapping Acr-dG adduct distribution at the nucleotide level in Acr-treated normal human bronchial epithelia (NHBE), we have found that the Acr-DNA binding spectrum in the p53 gene coincides with p53 mutational spectrum in lung cancer (19). Because ...

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Effect of Carcinogenic Acrolein on DNA Repair and Mutagenic Susceptibility

Wang

Tong

et al. 2012

Journal of Biological Chemistry

148

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“…Acrolein has been known as a toxic volatile organic compound and there are many comprehensive reviews on acrolein toxicity (Ghilarducci and Tjeerdema, 1995). Acrolein is highly toxic by chronic inhalation.…”

Section: Discussionmentioning

confidence: 99%

Determination of toxic carbonyl compounds in cigarette smoke

2006

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Toxic carbonyl compounds, including formaldehyde, malonaldehyde, and glyoxal, formed in mainstream cigarette smoke were quantified by derivatization-solid phase extraction-gas chromatography methods. Cigarette smoke from 14 commercial brands and one reference (2R1F) was drawn into a separatory funnel containing aqueous phosphate-buffered saline. Reactive carbonyl compounds trapped in the buffer solution were derivatized into stable nitrogen containing compounds (pyrazoles for -dicarbonyl and , -unsaturated aldehyde; quinoxalines for -dicarbonyls; and thiazolidines for alkanals). After derivatives were recovered using C 18 solid phase extraction cartridges, they were analyzed quantitatively by a gas chromatograph with a nitrogen phosphorus detector. The total carbonyl compounds recovered from regular size cigarettes ranged from 1.92 mg/cigarette À1 to 3.14 mg/cigarette À1 . The total carbonyl compounds recovered from a reference cigarette and a king size cigarette were 3.23 mg/cigarette À1 and 3.39 mg/cigarette À1 , respectively. The general decreasing order of the carbonyl compounds yielded was acetaldehyde (1110-2101 g/cigarette À1 ) > diacetyl (301-433 g/cigarette À1 ), acrolein (238-468 g/cigarette À1 ) > formaldehyde (87.0-243 g/cigarette À1 ), propanal (87.0-176 g/cigarette À1 ) > malonaldehyde (18.9-36.0 g/cigarette À1 ), methylglyoxal (13.4-59.6 g/cigarette À1 ) > glyoxal (1.93-6.98 g/cigarette À1 ).

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“…In addition to their carcinogenic effects, VOCs may also induce mucous membrane irritation (Bernstein et al 2008). Inhalation of acrolein and formaldehyde may result in local irritation in the respiratory tract (Ghilarducci and Tjeerdema 1995). Investigation of cultured human bronchial epithelial cells showed that exposure to dienaldehydes may induce oxidative stress, increased reactive oxygen species production, pro-inflammatory cytokines TNFα and IL-1β, and a decrease in GSH/GSSG ratio (glutathione status) (Chang et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Indoor air quality in a restaurant kitchen using margarine for deep-frying

Sofuoğlu

Toprak

İnal

et al. 2015

Environ Sci Pollut Res

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Indoor air quality has a great impact on human health. Cooking, in particular frying, is one of the most important sources of indoor air pollution. Indoor air CO, CO 2 , particulate matter (PM), and volatile organic compound (VOC) concentrations, including aldehydes, were measured in the kitchen of a small establishment where a special deepfrying margarine was used. The objective was to assess occupational exposure concentrations for cooks of such restaurants. While individual VOC and PM 2.5 concentrations were measured before, during, and after frying events using active sampling, TVOC, PM 10 , CO, CO 2 , temperature, and relative humidity were continuously monitored through the whole period. VOC and aldehyde concentrations did not increase to considerable levels with deep-frying compared to the background and public indoor environment levels, whereas PM 10 increased significantly (1.85 to 6.6 folds). The average PM 2.5 concentration of the whole period ranged between 76 and 249 μg/m 3 . Hence, considerable PM exposures could occur during deep-frying with the special margarine, which might be sufficiently high to cause health effects on cooks considering their chronic occupational exposures.

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Fate and Effects of Acrolein

Cited by 192 publications

References 137 publications

Effect of Carcinogenic Acrolein on DNA Repair and Mutagenic Susceptibility

Effect of Carcinogenic Acrolein on DNA Repair and Mutagenic Susceptibility

Determination of toxic carbonyl compounds in cigarette smoke

Indoor air quality in a restaurant kitchen using margarine for deep-frying

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