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Threshold for occluded formaldehyde patch test in formaldehyde-sensitive patients. Relationship to repeated open application test with a product containing formaldehyde releaser.

Our purpose was to investigate the eliciting threshold concentration of formaldehyde in formaldehyde-sensitive individuals in the occluded and non-occluded patch test, and to evaluate the relationship to repeated open application test (ROAT) with a product containing a formaldehyde releaser. 20 formaldehyde-sensitive patients and a control group of 20 healthy volunteers were included in the study. Occluded and non-occluded patch tests with formaldehyde solutions from 25 to 10,000 ppm, and ROAT for 1 week with a leave-on cosmetic product containing on average 300 ppm formaldehyde, were carried out simultaneously on each subject. In the occluded patch test, 1/2 of the 20 patients only reacted to 10,000 ppm formaldehyde, 9 reacted to 5,000 ppm, 3 reacted to 1,000 ppm, 2 reacted to 500 ppm and 1 reacted to 250 ppm. No definite positive reactions were observed in the non-occluded patch test or in the ROAT. No positive reactions were observed in the control group to any of the test procedures. We concluded that the threshold concentration for occluded patch test to formaldehyde in formaldehyde-sensitive patients was 250 ppm. The threshold in occluded patch test corresponded to the degree of sensitivity. Definite positive reactions in the ROAT were not seen, either indicating that they are unlikely to happen with the type of product used or that the exposure time was too short.

Adult↗

Identification of formaldehyde releasers and occurrence of formaldehyde and formaldehyde releasers in registered chemical products.

Substances referred to as formaldehyde releasers were identified on review of the literature. Information on product categories and typical concentrations for chemical products containing formaldehyde and formaldehyde releasers was obtained from the Danish Product Register Data Base (PROBAS). As of February 1992, 62,000 products were registered in PROBAS, 30,900 of these with information on composition and product category. Among the components of these products, 19 of the 22 identified formaldehyde releasers were found. The number of products registered with each formaldehyde releaser varied from 4 to 171, with cleaning agents, soaps, shampoos, paint/lacquers, and cutting fluids as the most frequent product categories. The most frequently registered formaldehyde releasers were bromonitropropanediol, bromonitrodioxane, and chloroallylhexaminium chloride. Formaldehyde itself was registered in 1,781 products, and was found in all product categories included in the study. It is concluded that products for industrial use as well as household and personal care products should be considered as sources of formaldehyde exposure. The use of unsystematic chemical names in literature is discussed.

Chemical Industry↗

Fluorescence of tryptophan-containing peptides on paper or silica gel after treatment with formaldehyde, formaldehyde-ozone or formaldehyde-hydrochloric acid.

Sensitive and specific procedures for the chromatographic detection of tryptophan and tryptophan-containing peptides are described. Formaldehyde gas induces strong and characteristic fluorescence from tryptophan and peptides with NH2-terminal tryptophan residues on silica gel. On filter-paper, the detection of small amounts of these compounds requires the additional use of an oxidant, such as ozone. Treatment with formaldehyde-hydrochloric acid was used as a method for inducing fluorescence from tryptophan-containing peptides regardless of the position of the tryptophan residue in the peptide molecule. This reaction is useful for the chromatographic demonstration of small amounts of such peptides on both paper and silica gel. The spectral properties of the fluorophores of such tryptophan-containing peptides are distinctive and serve to distinguish them from all other known biogenic compounds that are capable of giving fluorescence with formaldehyde.

Chromatography, Gel↗

[Effect of the interaction of formaldehyde and nitric oxide metabolism pathways in mechanism of their toxic action. I. Exo- and endogenous sources of formaldehyde and nitric oxide. Toxic action of formaldehyde].

Possible exogenous sources of formaldehyde and nitric oxide have been considered; the environment pollution conditions under which these compounds and their precursors have mutual effect on the organism; endogenous sources of FA and NO which are intermediates of the metabolism and key enzymes of their transformation (semicarbazide-sensitive amine oxidase and NO-synthase) the role of the C1 metabolic cycle pathways and methyl cycles in the FA formation and accumulation have been considered as well, various paths of FA toxic action have been characterized.

Animals↗

Urea-formaldehyde resins and free formaldehyde content.

Specifications of wood adhesives must be in correlation with the requirements for the corresponding wood products, for which they will be used. Formaldehyde emission of wood products bonded with urea-formaldehyde resin based adhesives is strictly regulated by standards and there is a compromise is between formaldehyde emission and performance, such as strength, or water resistance. Since values of formaldehyde emission depend on the test method used, in Europe urea-formaldehyde resins for adhesives may generally be classified according to HCHO emission in the particleboard rating of Emission 0 to Emission I class (E-0 to E-1). According to DIN EN 120, particleboard quality E1 emits <6.5 mg/100 g dry article determined with the perforator method. Although a great number of factors effect the formaldehyde emission of the cured products, such as the hardener system, the type of wood etc., the emission of formaldehyde is in strict correlation with the free formaldehyde content of the resin before the curing process. E1 emission class can be achieved, if the free formaldehyde content of the resin is lower than 0.2% by mass. Urea-formaldehyde resins containing. higher than 0.5% free formaldehyde by mass exceed emission class E2, and are not accepted. Since the free formaldehyde content of the urea-formaldehyde resin effects the emission of formaldehyde in the cured product, low formaldehyde content must be ensured during resin synthesis. This can be achieved by properly selecting synthesis conditions as well as raw materials. The quality of raw materials is an essential and determining factor for the synthesis of urea formaldehyde resins. The principal changes which may take place in the formaldehyde solution on storage are the polymerization and precipitation of the polymer, Cannizzaro reaction, methylal formation, oxydation to formic acid, condensation to hydroxyaldehydes and sugars. Any of these reactions are detrimental to product quality. The state of formaldehyde is also an essential factor, since the reaction of poly(methylene glycol)s with urea leads to methylene ether linkages resulting in emission of formaldehyde during storage and later on during the process of curing. Hydrolysis, isomerisation and decomposition of urea may take place simultaneously during improper storage conditions, such as high humidity, high temperatures, industrial atmosphere. The side products formed affect the reaction with formaldehyde during the synthesis resulting in high free formaldehyde content of urea-formaldehyde resins. The relation between synthesis conditions, free formaldehyde content and performance of urea-formaldehyde resins are discussed in detail.

Formaldehyde↗

Adaptation and acclimatization to formaldehyde in methylotrophs capable of high-concentration formaldehyde detoxification.

Formaldehyde is a highly toxic chemical common in industrial effluents, and it is also an intermediate in bacterial metabolism of one-carbon growth substrates, although its role as a bacterial growth substrate per se has not been extensively reported. This study investigated two highly formaldehyde-resistant formaldehyde utilizers, strains BIP and ROS1; the former strain has been used for industrial remediation of formaldehyde-containing effluents. The two strains were shown by means of 16S rRNA characterization to be closely related members of the genus Methylobacterium. Both strains were able to use formaldehyde, methanol and a range of multicarbon compounds as their principal growth substrate. Growth on formaldehyde was possible up to a concentration of at least 58 mM, and survival at up to 100 mM was possible after stepwise acclimatization by growth at increasing concentrations of formaldehyde. At such high concentrations of formaldehyde, the cultures underwent a period of formaldehyde removal without growth before the formaldehyde concentration fell below 60 mM, and growth could resume. Two-dimensional electrophoresis and MS characterization of formaldehyde-induced proteins in strain BIP revealed that the pathways of formaldehyde metabolism, and adaptations to methylotrophic growth, were very similar to those seen in the well-characterized methanol-utilizing methylotroph Methylobacterium extorquens AM1. Thus, it appears that many of the changes in protein expression that allow strain BIP to grow using high formaldehyde concentrations are associated with expression of the same enzymes used by M. extorquens AM1 to process formaldehyde as a metabolic intermediate during growth on methanol.

Acclimatization↗

Comparison of standard methods and gas chromatography method in determination of formaldehyde emission from MDF bonded with formaldehyde-based resins.

Formaldehyde emissions from MDF bonded with urea-formaldehyde resin (UF), melamine-formaldehyde resin (MF) and the co-polycondensation resin of urea-melamine-formaldehyde (UMF) and melamine-formaldehyde, measured by the Japanese standard method of determining formaldehyde emission with a desiccator (JIS A 5908) and the DIN EN 120 (European Committee For Standardization, 1991) method using the perforator value, were used as the typical standard methods. While the UF resin showed a desiccator value of 7.05 ppm and a perforator value of 12.1 mg/100 g panel, the MF resin exhibited a desiccator value of 0.6 ppm and a perforator value of 2.88 mg/100 g panel. According to the Japanese industrial standard and the European standard, the formaldehyde emission level of the MDF panels made with UF resin in this study was E(2) grade. The formaldehyde emission level was dramatically reduced by the addition of MF resin. This is because the addition of formaldehyde to melamine occurs more easily and completely than its addition to urea, even though the condensation reaction of melamine with formaldehyde is similar to that between urea and formaldehyde. These two methods, the desiccator method and the perforator method, produced proportionally equivalent results. Gas chromatography, a more sensitive and advanced method, was also used. The samples used for gas chromatography were gathered during the experiment involving the perforator method. The formaldehyde emission levels obtained from gas chromatography were similar to those obtained from the perforator method. The formaldehyde contents measured by gas chromatography were directly proportional to the perforator values.

Chemistry Techniques, Analytical↗

Correlation of regional formaldehyde flux predictions with the distribution of formaldehyde-induced squamous metaplasia in F344 rat nasal passages.

Squamous epithelium lines the nasal vestibule of the rat, rhesus monkey, and human. Respiratory, transitional, and olfactory epithelia line most areas posterior to the nasal vestibule. Inhaled formaldehyde gas induces squamous metaplasia posterior to the nasal vestibule and does not induce lesions in the nasal vestibule in rats and rhesus monkeys, indicating that squamous epithelium is resistant to irritant effects of formaldehyde and that squamous metaplasia may be an adaptive response. If squamous metaplasia is determined by formaldehyde dosimetry rather than by tissue-specific factors, squamous epithelium may be protective by absorbing less formaldehyde than other epithelial types. In a previous study, a three-dimensional, anatomically accurate computational fluid dynamics (CFD) model of the anterior F344 rat nasal passages was used to simulate inspiratory airflow and inhaled formaldehyde transport. The present study consisted of two related parts. First, the rat CFD model was used to test the hypothesis that the distribution of formaldehyde-induced squamous metaplasia is related to the location of high-flux regions posterior to squamous epithelium. Regional formaldehyde flux into nonsquamous epithelium predicted by the CFD model correlated with regional incidence of formaldehyde-induced squamous metaplasia on the airway perimeter of one cross-sectional level of the noses of F344 rats exposed to 10 and 15 ppm formaldehyde gas for 6 months. Formaldehyde flux into nonsquamous epithelium was estimated to vary by an order of magnitude depending on the degree of formaldehyde absorption by squamous epithelium. These results indicate that the degree to which squamous epithelium absorbs formaldehyde strongly affects the rate and extent of the progression of squamous metaplasia with continued exposure to formaldehyde. In the second part of this study, the CFD model was used to predict squamous metaplasia progression. Data needs for verification of this model prediction are considered. These results indicate that information on the permeability of squamous epithelium in rats, monkeys, and humans is important for accurate prediction of uptake in regions posterior to the nasal vestibule.

Administration, Inhalation↗

Exposure to gaseous formaldehyde induces IgE-mediated sensitization to formaldehyde in school-children.

BACKGROUND: Children attending a primary school showed symptoms such as headache, cough, rhinitis and epistaxis. Assessment of specific IgE to formaldehyde gave positive results in some children. OBJECTIVE: Was IgE-mediated sensitization as well as symptoms in children associated with formaldehyde exposure at school? METHODS: Sixty-two 8-year-old children attending three forms at a primary school were investigated. Indoor formaldehyde concentrations were measured in classrooms of both schools (one frame construction with particleboard used extensively as panelling vs a brick building) which were consecutively attended. Assessment of specific IgE to formaldehyde was done in all children. Children were transferred to a brick building and 3 months later specific IgE to formaldehyde in pupils showing initially elevated radioallergosorbent test (RAST) values reassessed. In all children symptoms were evaluated by questionnaire before and 3 months after changing school. RESULTS: In the school panelled with particleboard the World Health Organization (WHO) threshold for formaldehyde of 0.050 ppm was crossed in two classrooms (0.075 ppm and 0.069 ppm) whereas in one classroom 0.043 ppm was found. RAST classes of > or = 2 were found in three children, two of them attending the classroom with 0.075 ppm formaldehyde. Elevated RAST classes of > or = 1.3 were found in another 21 pupils. Thirty-eight pupils as well as 19 control children showed RAST classes in the normal range of < or = 1.2. Headache, nose bleeding, rhinitis, fatigue, cough, dry nasal mucosa and burning eyes were found in the affected children. There was a good correlation between symptoms and the formaldehyde concentrations in the classrooms. However, elevated IgE levels to formaldehyde did not correlate with symptoms. Formaldehyde concentrations in the classrooms of the brick built school were 0.029 ppm, 0.023 ppm and 0.026 ppm. After transferral specific IgE to formaldehyde decreased significantly from 1.7 +/- 0.5 to 1.2 +/- 0.2 (P < 0.002) as did the incidence of symptoms. CONCLUSION: Gaseous formaldehyde, besides its irritant action, leads to IgE-mediated sensitization. As children are more sensitive to toxic substances than adults, threshold levels for indoor formaldehyde should be reduced for children.

Air Pollution, Indoor↗

Reactions of formaldehyde plus acetaldehyde with deoxyguanosine and DNA: formation of cyclic deoxyguanosine adducts and formaldehyde cross-links.

We investigated the reactions of formaldehyde plus acetaldehyde with dGuo and DNA in order to determine whether certain 1,N(2)-propano-dGuo adducts could be formed. These adducts-3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-(3H)-one (1) and 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-(3H)-one (3a,b)-have been previously characterized as products of the reaction of acrolein with dGuo and DNA. Adduct 1 predominates in certain model lipid peroxidation systems [Pan, J., and Chung, F. L. (2002) Chem. Res. Toxicol. 15, 367-372]. We hypothesized that this could be due to stepwise reactions of formaldehyde and acetaldehyde with dGuo, rather than by reaction of acrolein with dGuo. The results demonstrated that adducts 1 and 3a,b were relatively minor products of the reaction of formaldehyde and acetaldehyde with dGuo and that there was no selectivity in their formation. These findings did not support our hypothesis. However, substantial amounts of previously unknown cyclic dGuo adducts were identified in this reaction. The new adducts were characterized by their MS, UV, and NMR spectra as diastereomers of 3-(2'-deoxyribosyl)-6-methyl-1,3,5-diazinan[4,5-a]purin-10(3H)-one (10a,b). Adducts 10a,b were apparently formed by addition of formaldehyde to N1 of N(2)-ethylidene-dGuo, followed by cyclization. An analogous set of four diastereomers of 3-(2'-deoxyribosyl)-6,8-dimethyl-1,3,5-diazinan[4,5-a]purin-10(3H)-one (12a-d) were formed in the reactions of acetaldehyde with dGuo. These products are the first examples of exocyclic dGuo adducts of the pyrimido[1,2-a]purine type in which an oxygen atom is incorporated into the exocyclic ring. Formaldehyde-derived adducts were the other major products of the reactions of formaldehyde plus acetaldehyde with dGuo. Prominent among these were N(2)-hydroxymethyl-dGuo (9) and the cross-link di-(N(2)-deoxyguaonosyl)methane (13). We did not detect adducts 1, 3a,b, or 10a,b in enzymatic hydrolysates of DNA that had been allowed to react with formaldehyde plus acetaldehyde. However, we did detect substantial amounts of the formaldehyde cross-links di-(N(6)-deoxyadenosyl)methane (17), with lesser quantities of (N(6)-deoxyadenosyl-N(2)-deoxyguanosyl)methane (18), di-(N(2)-deoxyguanosyl)methane (13), and N(6)-hydroxymethyl-dAdo (19). Schiff base adducts of formaldehyde and acetaldehyde were also detected in these reactions. These results demonstrate that the reactions of formaldehyde plus acetaldehyde with dGuo are dominated by newly identified cyclic adducts and formaldehyde-derived products whereas the reactions with DNA result in the formation of formaldehyde cross-link adducts. The carcinogens formaldehdye and acetaldehyde occur in considerable quantities in the human body and in the environment. Therefore, further research is required to determine whether the adducts described here are formed in animals or humans exposed to these agents.

Acetaldehyde↗

Formaldehyde cycle and the natural formaldehyde generators and capturers.

S-adenosyl-L-methionine serves as a methyl donor in virtually all of the vast number of enzymatic transmethylation reactions including DNA methylation. On the basis of our former experiences we questioned the formation of a methyl cation or methyl radical in the enzymatic transmethylation reactions. The formation of formaldehyde from the methyl moiety of S-adenosyl-L-methionine has been demonstrated. It became increasingly evident that there is a formaldehyde cycle in biological systems in which the formation of the methyl group of L-methionine takes place through formaldehyde and the formation of formaldehyde from S-adenosyl-L-methionine is linked to different enzymatic transmethylation reactions. It is also known that during demethylation processes both formaldehyde and demethylated compound can be formed. The abnormalities of the originally controlled formaldehyde cycle and the uncontrolled enzymatic production of formaldehyde from endogenous and/or exogenous substrates may be potential risk factors in pathogenesis of different disorders. The formaldehyde generator and capturer molecules may potentially normalise these abnormal processes. Trans-resveratrol (trans-3,5,4'-trihydroxystilbene), which is as phytoalexin, occurs naturally in grapes and a variety of medicinal plants. According to our present observations it is a natural concentration-dependent formaldehyde capture molecule. It would seem that elimination of the uncontrolled formaldehyde with resveratrol may exert a double effect in biological systems. The elimination of formaldehyde with resveratrol (first step) may cause a cardioprotective effect and the reaction products between resveratrol and formaldehyde (second step) may act as a chemopreventive factor against cancer.

Formaldehyde↗

The movement of blood formaldehyde in methanol intoxication. II. The movement of blood formaldehyde and its metabolism in the rabbit.

The movement of blood formaldehyde in rabbits that were intoxicated with methanol has been investigated by simple headspace gas chromatography-mass spectrometry for the microdetermination of formaldehyde in the blood. When methanol alone was administered to rabbits orally, formaldehyde could not be detected in the blood. Further, in an experiment on the metabolism of methanol in vitro, formaldehyde was not detected in specimen samples but formate was. In contrast, when methanol was orally administered to rabbits that had been pretreated with diethyldithiocarbamate (DDC), an aldehyde dehydrogenase (ALDH) inhibitor, 17 to 33 microM of formaldehyde were detected in the blood 4 hours later. However, formaldehyde was not detected in the blood when methanol was orally administered to rabbits that had been pretreated with pyrazole, an alcohol dehydrogenase (ADH) inhibitor. After rabbits were given an intravenous administration of formaldehyde, and on the addition of formaldehyde to a rabbit liver homogenate and blood, the formaldehyde in both instances was metabolized rapidly. Formaldehyde that was not metabolized within 10 to 15 minutes, however, bound to the tissue proteins. Therefore, according to the results of this study, formaldehyde was seen to be rapidly metabolized to formate without accumulating in the blood or binding to the tissue proteins. Formaldehyde thus appears to have little influence on the symptoms of methanol poisoning.

Animals↗

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students.

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.

Adult↗

Allergic contact dermatitis from formaldehyde. A case study focussing on sources of formaldehyde exposure.

Formaldehyde is a common contact allergen. The prognosis of formaldehyde-sensitive patients is generally considered to be bad because of widespread exposure to formaldehyde. 11 patients with eczema and a positive patch test to formaldehyde were interviewed by a dermatologist and a toxicologist/chemist and instructed to fill in a questionnaire on exposure to chemical products. The content of formaldehyde and formaldehyde releasers in such products was examined using the database of the Danish Product Register (PROBAS) and by supplemental inquiries of manufacturers or importers. All the patients used one or more products containing formaldehyde or formaldehyde releasers. Sources of exposure were cosmetics and personal care products, dishwashing liquids, water-based paints, photographic products, etc. Patients were advised to use alternatives to those products containing formaldehyde or formaldehyde releasers. The status of 10 out of the 11 patients' eczema at follow-up was about 1/3 healed, 1/3 improved and in 1/3 no change. When the relevance of positive patch test reactions to formaldehyde was based on information obtained on exposure, a very high rate of current relevance was found. Computerized data on product composition allows the screening of products for contact allergens and also generates lists of contact allergens indicated for patch testing, based on the patients' own products.

Adult↗

Effect of formaldehyde on the expression of adhesion molecules in nasal microvascular endothelial cells: the role of formaldehyde in the pathogenesis of sick building syndrome.

BACKGROUND: Formaldehyde is associated with sick building syndrome (SBS), a set of diffuse and irritative symptoms predominantly involving the eyes and the respiratory tract. However, its pathophysiological mechanism in SBS has not yet been clarified. OBJECTIVE: In this study we investigated the effect of formaldehyde on the expression of adhesion molecules on human mucosal microvascular endothelial cells (HMMECs). Furthermore, we investigated the effect of formaldehyde on adhesiveness of HMMECs to eosinophils. MATERIALS AND METHODS: HMMECs were incubated with various concentrations of formaldehyde (1 ng/mL-1 microg/mL) for 24 h, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) on HMMECs were evaluated by flow cytometry. The change in the expression of ICAM-1 and VCAM-1 mRNA was then evaluated by reverse transcriptase polymerase chain reaction. To understand the role of formaldehyde in eosinophilic inflammation of the nasal mucosa, we examined the effects of formaldehyde on the adhesiveness between HMMECs and eosinophils by eosinophil adhesion assay. RESULTS: Formaldehyde increased the surface expressions of ICAM-1 and VCAM-1 on HMMECs. Formaldehyde also induced ICAM-1 and VCAM-1 mRNA. In addition, the adhesiveness between HMMECs and eosinophils was also increased by formaldehyde. CONCLUSION: These in vitro studies suggest that formaldehyde may play a role as the irritant of the nasal mucosa by increasing the expressions of adhesion molecules on HMMECs and by enhancing the adhesiveness between HMMECs and eosinophils.

Cell Adhesion↗

Biological role of formaldehyde, and cycles related to methylation, demethylation, and formaldehyde production.

An overview is given on the analysis, formation, role and occurrence of formaldehyde in living organisms. Various methods have been used for the determination of formaldehyde in tissues and body fluids. Gas chromatography, thin-layer chromatography and HPLC were employed for the analysis of formaldehyde, mainly after derivatization. The formaldehyde level of human blood and urine was found at the low ppm level. The formaldehyde level could be increased upto several ten micro g/mL(-1) following special dietary supply. Biochemical pathway of both the formaldehyde production and demethylation/methylation processes is generally connected to the methionine - homocysteine cycles. Another important way of demethylation generated formaldehyde production is given by microsomal cytochrome P-450 dependent oxidation of xenobiotics, such as various drugs prescribed by doctors. Semicarbazide sensitive amine oxidase also produces formaldehyde. Increased level of formaldehyde may be the indication of either patho-physiological processes, or environmental contamination, or malnutrition. The formaldehyde-related methylation and demethylation procedures are also detailed. DNA methylation may have an important role in the pathogenesis of certain diseases.

Animals↗

Enhanced formaldehyde detoxification by overexpression of glutathione-dependent formaldehyde dehydrogenase from Arabidopsis.

The ADH2 gene codes for the Arabidopsis glutathione-dependent formaldehyde dehydrogenase (FALDH), an enzyme involved in formaldehyde metabolism in eukaryotes. In the present work, we have investigated the potential role of FALDH in detoxification of exogenous formaldehyde. We have generated a yeast (Saccharomyces cerevisiae) mutant strain (sfa1Delta) by in vivo deletion of the SFA1 gene that codes for the endogenous FALDH. Overexpression of Arabidopsis FALDH in this mutant confers high resistance to formaldehyde added exogenously, which demonstrates the functional conservation of the enzyme through evolution and supports its essential role in formaldehyde metabolism. To investigate the role of the enzyme in plants, we have generated Arabidopsis transgenic lines with modified levels of FALDH. Plants overexpressing the enzyme show a 25% increase in their efficiency to take up exogenous formaldehyde, whereas plants with reduced levels of FALDH (due to either a cosuppression phenotype or to the expression of an antisense construct) show a marked slower rate and reduced ability for formaldehyde detoxification as compared with the wild-type Arabidopsis. These results show that the capacity to take up and detoxify high concentrations of formaldehyde is proportionally related to the FALDH activity in the plant, revealing the essential role of this enzyme in formaldehyde detoxification.

Aldehyde Oxidoreductases↗