Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzo(a)pyrene or diethylnitrosamine

doi:10.1016/0277-5379(82)90020-7

European Journal of Cancer and Clinical Oncology

Volume 18, Issue 1, January 1982, Pages 13-21, 23-31

European Journal of ...

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Abstract

Syrian golden hamsters were exposed to 0 or 2500–1650 ppm acetaldehyde vapour, 7 hr/day, 5 days/week for a period of 52 weeks. A proportion of the animals was given, simultaneously, either intratracheal instillations of benzo(a) pyrene (BP) or subcutaneous injections of diethylnitrosamine (DENA). All treatments were stopped after 52 weeks. The study was terminated after 81 weeks. Major effects attributed to acetaldehyde exposure included growth retardation, rhinitis, hyperplasia and metaplasia of the nasal, laryngeal and tracheal epithelium, nasal and laryngeal carcinomas, and a markedly increased incidence of BP-initiated tracheobronchial carcinomas. There was no evidence of acetaldehyde enhancing the development of DENA-initiated tumours of the respiratory tract. It was concluded that acetaldehyde is an irritant, as well as a carcinogen, for the respiratory tract of Syrian golden hamsters. Possible mechanisms of the carcinogenicity of this aldehyde are briefly discussed.

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It was also clastogenic (caused chromosome damage) in vitro and in vivo. Acetaldehyde induced localized nasal and larynx tumors in animal inhalation studies, but no tumors in an oral rat study (Feron et al., 1982; Soffritti et al., 2002; Woutersen et al., 1986). However, there is strong evidence for a non-linear dose-response for the mutagenic and carcinogenic effects, with cytotoxicity/DNA adducts occurring only after saturation of detoxification mechanisms (Albertini, 2013).
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Aldehydes are strong electrophiles that can undergo addition reactions with thiols and amines to form toxic adducts in cellular proteins, including DNA–protein cross-links. Aldehydes occur naturally in cells and are generated during intermediary metabolism of natural compounds, drugs, and xenobiotics. Volatile aldehydes, including formaldehyde, acetaldehyde, and acrolein, are found in tobacco smoke, combustion engine exhaust, and as industrial pollutants. Occupational exposures occur in industries that manufacture resins, wood products, paper, textiles, carpet, and leather goods. Aldehydes are metabolized primarily by dehydrogenases or glutathione-dependent pathways, and toxicity results from overwhelming of these cellular detoxification systems. The mucosal lining of nasopharyngeal tissues is the primary target of inhaled formaldehyde, with a reported association between exposure and nasopharyngeal carcinomas. Both genotoxic and cytotoxic effects have been documented in nasal tissues of rodents and primates following formaldehyde inhalation exposure. Risk assessment for carcinogenic potential of inhaled formaldehyde and acetaldehyde has traditionally used DNA–protein cross-links as a biomarker and surrogate for tissue-specific exposure patterns. Recent evidence suggests that cytotoxicity-dependent regenerative cellular proliferation may be a more reliable index and genotoxic end point for low-level formaldehyde exposures. DNA–protein cross-links are transient in nature, and the exact biochemical mechanisms involved in aldehyde-induced carcinogenesis are unclear.
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^☆: The investigations were supported by a grant from the research fund of the Scientific Advisory Committee Smoking and Health. This fund has been established by the Dutch Cigarette Industry Foundation. Preliminary results of this study were presented in the form of a poster during the Symposium on ‘Cocarcinogenicity and Biological Effects of Tumor Promoters’, Castle of Elmau, Klais, Federal Republic of Germany, 1980.

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European Journal of Cancer and Clinical Oncology

Abstract

References (15)

Effects of exposure to furfural vapour in hamsters simultaneously treated with benzo(a)pyrene or diethylnitrosamine

Toxicology

Acetaldehyde induces cross-links in DNA and causes sister-chromatid exchanges in human cells

Mutat Res

Acetaldehyde, but not ethanol, induces sister-chromatid exchanges in Chinese hamster cells in vitro

Mutat Res

Vapor phase analysis of tobacco smoke

Tobacco Sci

Flüchtige Inhaltsstoffe des Tabaksrauches

Studies on the effects of acetaldehyde in tissue cells cultivated in vitro

Cancer Res

Effects inhibitoires de la fumée de tabac sur l'activité ciliaire de l'épithélium respiratoire et nature des composants responsables

Bull Acad Natl Med (Paris)

Cited by (134)

Investigations on the new mechanism of action for acetaldehyde-induced clastogenic effects in human lung fibroblasts

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides

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Aldehydes

Key role of local acetaldehyde in upper GI tract carcinogenesis

ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde

Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzo(a)pyrene or diethylnitrosamine☆

Abstract

Toxicology

Mutat Res

Mutat Res

Vapor phase analysis of tobacco smoke

Tobacco Sci

Flüchtige Inhaltsstoffe des Tabaksrauches

Studies on the effects of acetaldehyde in tissue cells cultivated in vitro

Cancer Res

Effects inhibitoires de la fumée de tabac sur l'activité ciliaire de l'épithélium respiratoire et nature des composants responsables

Bull Acad Natl Med (Paris)