2-butenal and Neoplasms

Topics: Acrolein; Aldehydes; Animals; Arecoline; Carcinogenicity Tests; Carcinogens, Environmental; Consensus Development Conferences as Topic; Environmental Exposure; Humans; Internet; Neoplasms; Risk Assessment; Telecommunications

DNA damage is one of the leading causes of various pathological conditions including carcinogenesis. Crotonaldehyde is a 4-carbon unsaturated bifunctional aldehyde which is found ubiquitously and produced both exogenously and endogenously. It reacts with deoxyguanosine and form adducts with DNA. These adducts were detected and found involved in tumor formation in rats treated with crotonaldehyde. In the present study, structural changes in DNA by crotonaldehyde were evaluated by Fourier transform infrared (FTIR) spectroscopy, differential scanning colorimetry (DSC), dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), and atomic force microscopy (AFM). Enhanced binding was observed in cancer autoantibodies with the DNA modified by crotonaldehyde than the native counterpart. Immunological studies revealed enhanced binding of cancer autoantibodies with crotonaldehyde modified DNA, compared to the native form. Furthermore, lymphocyte DNA isolated from cancer patients demonstrated considerable recognition of anti-Cro-DNA IgG as compared to the DNA from healthy individuals. Therefore, we suggest that crotonaldehyde modified DNA presents unique epitopes, that may trigger autoantibody induction in cancer patients.

Topics: Adult; Aldehydes; Autoantibodies; DNA; Epitopes; Female; Humans; Immunoglobulin G; Male; Middle Aged; Neoplasms

This paper summarizes our recent studies on adducts produced in the reactions of the carcinogens crotonaldehyde (2-butenal) and acetaldehyde with deoxyguanosine (dG) and DNA. Human exposure to these carcinogens can be considerable, from both exogenous and endogenous sources. Crotonaldehyde reacts with DNA to form Michael addition products, a pathway that has been well described. We describe a second major pathway, in which 3-hydroxybutanal, formed by addition of H(2)O to crotonaldehyde, reacts with DNA to produce the Schiff base N(2)-(3-hydroxybut-1-ylidene)dG as well as several diastereomers of N(2)-paraldol-dG. Acetaldehyde reacts with DNA and dG giving a major Schiff base adduct, N(2)-ethylidene-dG. A cross-linked adduct of acetaldehyde has been characterized for the first time, and other adducts resulting from the reaction of two and three molecules of acetaldehyde with dG have been observed. The results of these studies demonstrate that some structurally unique adducts are formed from these carcinogenic aldehydes and suggest some new directions for research on the potential role of aldehydes in human cancer.

Topics: Acetaldehyde; Aldehydes; Carcinogens; Chemical Phenomena; Chemistry; Deoxyguanosine; DNA Adducts; Humans; Neoplasms

Crotonaldehyde and 2-hexenal are bifunctional compounds that form 1,N2-propanodeoxyguanosine adducts and are mutagenic and genotoxic; crotonaldehyde is carcinogenic. Analysis of the mutations resulting from crotonaldehyde-induced DNA damage revealed the importance of deoxyguanosine adducts. Humans are exposed ubiquitously to these compounds by various routes. The highest daily intake of crotonaldehyde is assumed to be derived from cigarette smoke (31-169 micrograms/kg body weight), and the highest intake of 2-hexenal is probably from fruit and vegetables (31-165 micrograms/kg body weight per day). Because these compounds are suspected to play on important role in carcinogenicity, we developed sensitive 32P-postlabelling techniques for DNA adducts of crotonaldehyde and hexenal, in order to improve estimates of cancer risk. The respective standards were also synthesized and characterized spectroscopically. We report here the results of the 32P-postlabelling, e.g. the stability of the adducts in respect of nuclease P1 treatment, their labelling efficiencies, thin-layer chromatography of adduct spots and the recoveries and detection limits. In untreated male Fischer 344 rats, neither crotonaldehyde nor 2-hexenal adducts were detected, but crotonaldehyde adducts were found in the tissues of rats given single doses of 200 or 300 mg/kg body weight and in the livers of rats after repeated doses of 1 or 10 mg/kg body weight. The adduct levels were higher 20 h after gavage than after 12 h. The adducts persist to a certain extent. 2-Hexenal adducts were detected in tissues of male Fischer 344 rats after gavage with single doses of 50, 200 or 500 mg/kg body weight. The highest adduct levels were measured 48 h after gavage, but no adducts were found 8 h after gavage. Two approaches for cancer risk estimation are discussed. One is based on the correlation between the covalent binding index, calculated from adduct levels, and the median toxic dose (TD50) (Lutz, 1986) and showed a cancer risk of 1 per 10(7) lives for hexenal, assuming dietary intakes of 31-165 micrograms/kg body weight per day. The other is based on a cancer incidence of 0.07 at a dose of crotonaldehyde of 4.2 mg/kg body weight per day assessed from the study of Chung et al. (1986), which can be interpreted as a risk of 5.8-18 new cases per 10(4) smokers, assuming a consumption of 30 cigarettes per day. The latter approach may, however, lead to an overestimate of the cancer risk associated with exposure

Topics: Adenosine Triphosphate; Aldehydes; Animals; Carcinogens; Chromatography, Thin Layer; Deoxyguanosine; Diet; DNA Adducts; DNA Damage; Dose-Response Relationship, Drug; Humans; Hydrogen-Ion Concentration; Kinetics; Liver; Male; Models, Chemical; Mutagens; Neoplasms; Polynucleotide 5'-Hydroxyl-Kinase; Rats; Rats, Inbred F344; Risk Assessment; Tissue Distribution