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PubMed2006

The implausibility of systemic genotoxic effects measured by the comet assay in rats exposed to formaldehyde.

A recent publication reported genotoxic effects in the alkaline comet assay in lymphocytes and liver cells of rats exposed to formaldehyde (FA) by inhalation (Im,H.; et al. J. Proteome Res. 2006, 5, 1354-1366). Rats were exposed to 5 and 10 ppm FA for 2 weeks in inhalation chambers. A similar dose-related increase in DNA migration was measured in both cell types. These results are inconsistent with published data concerning FA toxicity: (i) Systemic genotoxic effects are reported, whereas previous animal experiments indicated only local effects. (ii) Similar effects were observed in liver cells and lymphocytes despite administration by inhalation. (iii) Increased DNA migration was measured, whereas FA-induced DNA-protein cross-links (DPX) should reduce DNA migration. These three aspects are critically discussed, and the plausibility of the results published by Im and colleagues is questioned.

Animals↗
PubMed2004

Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses.

The proposed use of methanol (H3COH) as an alternative to fossil fuels has prompted concern about potential health risks resulting from widespread environmental exposure. Methanol is teratogenic in rodents and, although the exact toxic species is not known, teratogenesis may result from the enzymatic biotransformation of H3COH to formaldehyde (CH2O) and formic acid causing increased biological reactivity and toxicity. A protective role for the antioxidant glutathione (GSH) has been described for H3COH, CH2O and formic acid toxicity in various biological systems but has yet to be evaluated in the developing conceptus. Whole embryo culture studies were conducted using GD 10-11 rat conceptuses to elucidate the relationship between H3COH and its metabolites and GSH status. Methanol exposure produced a decrease in normal growth parameters and a dose-dependent loss of viability. CH2O had deleterious effects on embryo growth and viability. Sodium formate (HCOONa) exposure resulted in a high mortality rate but viable embryos did not manifest any abnormalities. Methanol, CH2O, and HCOONa all produced a significant depletion of GSH in both embryo and VYS. Inhibition of GSH synthesis by L-buthionine-S,R-sulfoximine (BSO) treatment exacerbated H3COH, CH2O and HCOONa embryotoxicity. Interestingly, only H3COH/BSO and CH2O/BSO co-treatments caused increased malformation, while embryos treated with HCOONa/BSO did not produce any developmental deformities. These results implicate CH2O as the most embryotoxic H3COH metabolite, on a molar basis, in terms of causing dysmorphogenesis, alterations of normal growth parameters and embryolethality. HCOONa was selectively embryolethal and did not produce dysmorphogenesis. CH2O toxicity is potentiated by GSH depletion, indicating that GSH may be more directly involved in its detoxication in the embryo.

Animals↗
PubMed2003

The prevalence of IgE sensitization to formaldehyde in asthmatic children.

BACKGROUND: Formaldehyde (FA) is well documented as a cause of occupational asthma. Recently, attention has been paid to FA as an allergen and a pollutant that enhances allergic sensitization. We have investigated the prevalence of FA-specific IgE in asthmatic children and the correlation between IgE sensitization to FA and the severity of asthma. METHODS: One hundred and fifty-five children were investigated, 122 of them asthmatic and 33 nonallergic. Specific IgE against FA was measured by CAP RAST. In addition, the patients answered a questionnaire, containing questions on clinical features of their asthma, their living conditions, and symptoms of mucosal irritation. RESULTS: Of all the subjects assessed, FA-specific IgE was detected in only two asthmatics, and their IgE levels of FA were low (0.42 and 0.46 UA/ml). One of the two patients with FA-specific IgE had severe asthma and frequent symptoms of mucosal irritation, but the other had mild asthma and only rare symptoms of mucosal irritation. CONCLUSIONS: The prevalence of IgE sensitization to FA appears very low in Japanese children, whether or not they have asthma. Therefore, it appears likely that FA is not one of the major allergens causing childhood asthma.

Adolescent↗
PubMed2001

Real-time monitoring of formaldehyde-induced DNA-lysozyme cross-linking with piezoelectric quartz crystal impedance analysis.

A novel method for monitoring, in real time, the formaldehyde (FA)-induced DNA-protein cross-linking process with the piezoelectric quartz crystal impedance (PQCI) technique is proposed. The method was used to monitor FA-induced DNA-lysozyme cross-link formation. Lysozyme was directly immobilized on the silver electrode surface of a piezoelectric quartz crystal by adsorption. The lysozyme-coated piezoelectric sensor was in contact with FA and DNA solutions. The time courses of the resonant frequency and equivalent circuit parameters of the sensor during the cross-linking were simultaneously obtained and are discussed in detail. On the basis of the feature of the multi-dimensional information provided by the PQCI technique, it was concluded that the observed frequency decrease could be mainly ascribed to the mass increase resulting from the cross-linking. According to the frequency decrease with time, the kinetics of the cross-linking process were quantitatively studied. A piezoelectric response model for the cross-linking was theoretically derived. Fitting the experimental data to the model, the kinetic parameters, such as the binding and dissociation rate constants (k(1) and k(-1)) and the cross-linking equilibrium constant (Ka), were determined. At 37 degrees C, the k(1), k(-1) and Ka values obtained were 7.0 (+/-0.1) x 10(-5) (microg ml(-1))(-1) s(-1), 6.6 (+/-0.1) x 10(-3) s(-1) and 1.06 (+/-0.02) x 10(-2) (microg ml(-1))(-1), respectively.

DNA↗
PubMed2001

Application of an integrated prepstation-GC-NPD system to automated continuous measurement of formaldehyde and acetaldehyde in the atmosphere.

An integrated PrepStation-gas chromatography-nitrogen phosphorus detection (GC-NPD) system was used for the fully automated, continuous, low parts per billion analysis of lower aldehydes in the atmosphere. Analysis involved a solid phase extraction procedure based on the collection of aldehydes from air pumped through a silica gel cartridge impregnated with acidified 2,4-dinitrophenylhydrazine (DNPH). Automated continuous measurements were performed with a typical temporal resolution of 3 h, including 146 min for sampling of air at a constant air flow rate of 0.15 L min(-1) and 34 min for the preparation and extraction of several cartridges. Analysis of samples could be performed in parallel by using previously defined scheduler settings from separate, independent software to operate the PrepStation module. GC-NPD measurements were highly repeatable, and relative standard deviations were < 3.0%. Recoveries for all compounds were 88-101%. DNPH decomposition products did not adversely affect the quantitative determination of aldehyde DNPHs; therefore, it was not necessary to remove excess DNPH reagent. The limits of quantification (10sigma of the blank hydrazones) of formaldehyde and acetaldehyde were 2.2 and 1.2 ppb, respectively, for 21.9 L (0.15 L min(-1) for 146 min) of air sample volume. The integrated PrepStation GC-NPD system gave results comparable to those of the Sep-Pak DNPH silica cartridge method.

Air Pollutants↗
PubMed2005

New insights on reaction dynamics from formaldehyde photodissociation.

We review the photodissociation dynamics of formaldehyde with an emphasis on recent calculations that make use of a global ab initio-based potential energy surface for the S(0) state. These calculations together with recent experiments reveal striking departures from conventional transition state theory for the formation of the molecular products H(2) + CO. The evidence for this departure is reviewed in detail by examining properties of the new potential surface and results of quasiclassical trajectory dynamics calculations using this surface. We also review very recent work on the dynamics governing the formation of radical products, H + HCO. These products can be formed on the T(1) surface as well as the S(0) one, and we present some results contrasting the dynamics on these two surfaces. This work makes use of a new semi-global ab initio-based T(1) potential energy surface.

Formaldehyde↗
PubMed2006

The impact of domestic wood burning on personal, indoor and outdoor levels of 1,3-butadiene, benzene, formaldehyde and acetaldehyde.

The aim of this study was to quantify personal exposure and indoor levels of the suspected or known carcinogenic compounds 1,3-butadiene, benzene, formaldehyde and acetaldehyde in a small Swedish town where wood burning for space heating is common. Subjects (wood burners, n = 14), living in homes with daily use of wood-burning appliances were compared with referents (n = 10) living in the same residential area. Personal exposure and stationary measurements indoors and at an ambient site were performed with diffusive samplers for 24 h. In addition, 7 day measurements of 1,3-butadiene and benzene were performed inside and outside the homes. Wood burners had significantly higher median personal exposure to 1,3-butadiene (0.18 microg m(-3)) compared with referents (0.12 microg m(-3)), which was also reflected in the indoor levels. Significantly higher indoor levels of benzene were found in the wood-burning homes (3.0 microg m(-3)) compared with the reference homes (1.5 microg m(-3)). With regard to aldehydes, median levels obtained from personal and indoor measurements were similar although the four most extreme acetaldehyde levels were all found in wood burners. High correlations were found between personal and indoor levels for all substances (r(s) > 0.8). In a linear regression model, type of wood-burning appliance, burning time and number of wood replenishments were significant factors for indoor levels of 1,3-butadiene. Domestic wood burning seems to increase personal exposure to 1,3-butadiene as well as indoor levels of 1,3-butadiene and benzene and possibly also acetaldehyde. The cancer risk from these compounds at exposure to wood smoke is, however, estimated to be low in developed countries.

Acetaldehyde↗
PubMed1988

Formaldehyde adducts of glutathione. Structure elucidation by two-dimensional n.m.r. spectroscopy and fast-atom-bombardment tandem mass spectrometry.

Aqueous mixtures of formaldehyde and glutathione react to form a variety of cyclized adducts in addition to S-hydroxymethylglutathione. The adducts are in labile equilibrium with each other and are not readily separated. The structures of two of the other major adducts were determined by concerted application of 13C-1H two-dimensional chemical-shift correlation, fast-atom-bombardment mass spectrometry and tandem mass spectrometry to the adduct mixtures in aqueous solution.

Chemical Phenomena↗
PubMed1989

Intracellular transport of formaldehyde-treated serum albumin in liver endothelial cells after uptake via scavenger receptors.

Endocytosis of formaldehyde-treated serum albumin (FSA) mediated by the scavenger receptor was studied in rat liver endothelial cells. Suspended cells had about 8000 receptors/cell, whereas cultured cells had about 19,000 receptors/cell. Kd was 10(-8) M in both systems. Cell-surface scavenger receptors were found exclusively in coated pits by electron microscopy, by using ligand labelled with colloidal gold. Cell-surface-bound FSA could be released by decreasing the pH to 6.0; it was therefore possible to assess the rate of internalization of surface-bound ligand. This rate was very high: t1/2 for internalization of ligand prebound at 4 degrees C was 24 s. The endocytic rate constant at 37 degrees C, Ke, measured as described by Wiley & Cunningham [(1982) J. Biol. Chem. 257, 4222-4229], was 2.44 min-1, corresponding to t1/2 = 12 s. Uptake of FSA at 37 degrees C after destruction of one cell-surface pool of receptors by Pronase was decreased to 60%. This finding is compatible with a relatively large intracellular pool of receptors. The intracellular handling of 125I-tyramine-cellobiose-labelled FSA (125I-TC-FSA) was studied by subcellular fractionation in sucrose gradients, Nycodenz gradients or by differential centrifugation. The density distributions of degraded and undegraded 125I-TC-FSA after fractionation of isolated non-parenchymal cells and whole liver were similar, when studied in Nycodenz and sucrose gradients, suggesting that the subcellular distribution of the ligand was not influenced by the huge excess of non-endothelial material in a whole liver homogenate. Fractionation in sucrose gradients showed that the ligand was sequentially associated with organelles banding at 1.14, 1.17 and 1.21 g/ml. At 9-12 min after intravenous injection the ligand was in a degradative compartment, as indicated by the accumulation of acid-soluble radioactivity at 1.21 g/ml. A rapid transfer of ligand to the lysosomes was also indicated by the finding that a substantial proportion of the ligand could be degraded by incubating mitochondrial fractions prepared 12 min after intravenous injection of the ligand. The results indicate that FSA is very rapidly internalized and transferred through an endosomal compartment to the lysosomes. The endosomes are gradually converted into lysosomes between 9 and 12 min after injection of FSA. The rate-limiting step in the intracellular handling of 125I-TC-FSA is the degradation in the lysosomes.

Animals↗
PubMed2002

Contact dermatitis to phenol-formaldehyde resin in two plywood factory workers.

Two cases of occupational allergic contact dermatitis in plywood mill workers are presented. Although both patients thought they were allergic to sawdust, they were in fact allergic to a phenol-formaldehyde resin used to bond the plywood sheets together. Both patients only developed their dermatitis when they came into contact with uncured glue.

Adult↗
PubMed2000

RAPD-fingerprinting of Serratia marcescens after formaldehyde inactivation of DNase activity.

Serratia marcescens strains commonly cause hospital outbreaks. A random amplified polymorphic DNA (RAPD) assay was applied to the epidemiology of Ser. marcescens using formaldehyde fixation and boiling of bacterial cells for DNA extraction. The method preserved bacterial DNA and gave optimal results of RAPD-fingerprinting, facilitating the investigation of hospital infections caused by Ser. marcescens.

DNA Fingerprinting↗
PubMedDate not supplied

Formaldehyde in the pathogenesis of hemodialysis-related anti-N antibodies.

The role of formaldehyde (CH2O) in the pathogenesis of anti-N-like antibodies found in patients on chronic hemodialysis was investigated. In vitro studies were performed by incubating MM cells in varying concentrations of CH2O for variable time periods, corresponding to conditions that occur in dialysis. This MM cells acquired reactivity to anti-N antibody. The antigenic shift is felt to occur from the interaction of CH2O with the terminal N-acetylneuraminic acid (sialic acid) groups of M substance, resulting in the exposure to an altered-N antigen that is immunogenically active. Through a similar mechanism, CH2O may also directly modify N substance.

Antibodies↗
PubMedDate not supplied

Reduced antibody response in patients with chronic renal failure undergoing hemodialysis with formaldehyde sterilized units.

In an attempt to explain the relatively low incidence of antibody production seen in patients undergoing regular hemodialysis, sera from 200 patients were exposed to formaldehyde under conditions similar to those during dialysis. It was found that this procedure substantially reduced antibody titers, except when the initial titer was very high. The danger of missing low antibody titers after dialysis is pointed out.

ABO Blood-Group System↗
PubMed2002

Contact allergy to o-cresol--a sensitizer in phenol-formaldehyde resin.

BACKGROUND: In patients hypersensitive to phenol formaldehyde resin (PFR) it is, for therapeutic and preventive reasons, important to know the identity of the primary sensitizing substances, their sensitizing capacity, as well as their cross-reaction patterns. When elucidating the issue of cross reactivity in patients with contact allergy to simple methylol phenols (MP), o-cresol was shown to be a contact sensitizer. Besides cross reactivity, contamination of one or more MP(s) in o-cresol as well as o-cresol being a sensitizer of its own in PFR were possible explanations of the simultaneous positive patch test reactions to MP and o-cresol. OBJECTIVE: The aim of this study was to investigate if the simultaneous allergic reactions to PFR and o-cresol could be explained by the presence of this substance in PFR. METHODS: Patch testing, high-pressure liquid chromatography (HPLC), nuclear magnetic resonance spectrometry (NMR), gas chromatography (GC), and mass spectrometry (MS) were used. RESULTS: o-Cresol was isolated from the specific PFR used in our standard patch test series and identified. The concentration in the resin was 0.066% wt/wt. CONCLUSION: The current study establishes o-cresol as a contact sensitizer in a PFR. The observed reactions to o-cresol could be on the basis of cross reactivity or primary sensitization.

Allergens↗
PubMed2006

Formaldehyde exposure in a gross anatomy laboratory--personal exposure level is higher than indoor concentration.

GOAL, SCOPE AND BACKGROUND: Cadavers for gross anatomy laboratories are usually prepared by using embalming fluid which contains formaldehyde (FA) as a principal component. During the process of dissection, FA vapors are emitted from the cadavers, resulting in the exposure of medical students and their instructors to elevated levels of FA in the laboratory. The American Conference of Governmental Industrial Hygienists (ACGIH) has set a ceiling limit for FA at 0.3 ppm. In Japan, the Ministry of Health, Labour and Welfare has set an air quality guideline defining two limit values for environmental exposure to FA: 0.08 ppm as an average for general workplaces and 0.25 ppm for specific workplaces such as an FA factory. Although there are many reports on indoor FA concentrations in gross anatomy laboratories, only a few reports have described personal FA exposure levels. The purpose of the present study was to clarify personal exposure levels as well as indoor FA concentrations in our laboratory in order to investigate the relationship between them. METHODS: The gross anatomy laboratory was evaluated in the 4th, 10th and 18th sessions of 20 laboratory sessions in total over a period of 10 weeks. Air samples were collected using a diffusive sampling device for organic carbonyl compounds. Area samples were taken in the center and four corners of the laboratory during the entire time of each session (4-6 hours). Personal samples were collected from instructors and students using a sampling device pinned on each person's lapel, and they were 1.1 to 6 hours in duration. Analysis was carried out using high performance liquid chromatography. RESULTS AND DISCUSSION: Room averages of FA concentrations were 0.45, 0.38 and 0.68 ppm for the 4th, 10th and 18th sessions, respectively, ranging from 0.23 to 1.03 ppm. These levels were comparable to or relatively lower than the levels reported previously, but were still higher than the guideline limit for specific workplaces in Japan and the ACGIH ceiling limit. The indoor FA concentrations varied depending on the contents of laboratory sessions and seemed to increase when body cavity or deep structures were being dissected. In all sessions but the 4th, FA levels at the center of the room were higher than those in the corners. This might be related to the arrangement of air supply diffusers and return grills. However, it cannot be ruled out that FA levels in the corners were lowered by leakage of FA through the doors and windows. Average personal exposure levels were 0.80, 0.45 and 0.51 ppm for instructors and 1.02, 1.08 and 0.89 ppm for students for the 4th, 10th and 18th session, respectively. The exposure levels of students were significantly higher than the mean indoor FA concentrations in the 4th and 10th sessions, and the same tendency was also observed in the 18th session. The personal exposure level of instructors was also significantly higher than the indoor FA level in the 4th session, while they were almost the same in the 10th and 18th sessions. Differences in behavior during the sessions might reflect the differential personal exposure levels between students and instructors. CONCLUSION: The present study revealed that, if a person is close to the cadavers during the gross anatomy laboratory, his/her personal exposure level is possibly 2 to 3-fold higher than the mean indoor FA concentration. This should be considered in the risk assessment of FA in gross anatomy laboratories. RECOMMENDATION AND OUTLOOK: If the risk of FA in gross anatomy laboratories is assessed based on the indoor FA levels, the possibility that personal exposure levels are 2 to 3-fold higher than the mean indoor FA level should be taken into account. Otherwise, the risk should be assessed based on the personal exposure levels. However, it is hard to measure everyone's exposure level. Therefore, further studies are necessary to develop a method of personal exposure assessment from the indoor FA concentration.

Air Pollution, Indoor↗
PubMed2000

In organello formaldehyde crosslinking of proteins to mtDNA: identification of bifunctional proteins.

The segregating unit of mtDNA is a protein-DNA complex called the nucleoid. In an effort to understand how nucleoid proteins contribute to mtDNA organization and inheritance, we have developed an in organello formaldehyde crosslinking procedure to identify proteins associated with mtDNA. Using highly purified mitochondria, we observed a time-dependent crosslinking of protein to mtDNA as determined by sedimentation through isopycnic cesium chloride gradients. We detected approximately 20 proteins crosslinked to mtDNA and identified 11, mostly by mass spectrometry. Among them is Abf2p, an abundant, high-mobility group protein that is known to function in nucleoid morphology, and in mtDNA transactions. In addition to several other proteins with known DNA binding properties or that function in mtDNA maintenance, we identified other mtDNA-associated proteins that were not anticipated, such as the molecular chaperone Hsp60p and a Krebs cycle protein, Kgd2p. Genetic experiments indicate that hsp60-ts mutants have a petite-inducing phenotype at the permissive temperature and that a kgd2Delta mutation increases the petite-inducing phenotype of an abf2Delta mutation. Crosslinking and DNA gel shift experiments show that Hsp60p binds to single-stranded DNA with high specificity for the template strand of a putative origin of mtDNA replication. These data identify bifunctional proteins that participate in the stability of rho(+) mtDNA.

Cell Fractionation↗
PubMed1985

Formaldehyde-mediated DNA-protein crosslinking: a probe for in vivo chromatin structures.

Formaldehyde (HCHO) produces DNA-protein crosslinks both in vitro and in vivo. Simian virus 40 (SV40) chromosomes that have been fixed by prolonged incubation with HCHO either in vitro or in vivo (within SV40-infected cells) can be converted to nearly protein-free DNA by limit-digestion with Pronase in the presence of NaDodSO4. The remaining Pronase-resistant DNA-peptide adducts retard the DNA upon gel electrophoresis, allowing resolution of free and crosslink-containing DNA. Though efficiently crosslinking histones to DNA within nucleosomes both in vitro and in vivo, HCHO does not crosslink either purified lac repressor to lac operator-containing DNA or an (A + T)-DNA-binding protein (alpha-protein) to its cognate DNA in vitro. Furthermore, a protein that does not bind to DNA, such as serum albumin, is not crosslinked to DNA by HCHO even at extremely high protein concentrations. These properties of HCHO as a DNA-protein crosslinker are used to probe the distribution of nucleosomes in vivo. We show that there are no HCHO-crosslinkable DNA-protein contacts in a subset of SV40 chromosomes in vivo within a 325-base-pair stretch that spans the "exposed" (nuclease-hypersensitive) region of the SV40 chromosome. This replication origin-proximal region has been found previously to lack nucleosomes in a subset of isolated SV40 chromosomes. We discuss other applications of the HCHO technique, including the possibility of obtaining base-resolution in vivo nucleosome "footprints."

Animals↗
PubMed1996

Pea formaldehyde-active class III alcohol dehydrogenase: common derivation of the plant and animal forms but not of the corresponding ethanol-active forms (classes I and P).

A plant class III alcohol dehydrogenase (or glutathione-dependent formaldehyde dehydrogenase) has been characterized. The enzyme is a typical class III member with enzymatic parameters and substrate specificity closely related to those of already established animal forms. Km values with the pea enzyme are 6.5 microM for NAD+, 2 microM for S-hydroxymethylglutathione, and 840 microM for octanol versus 9, 4, and 1200 microM, respectively, with the human enzyme. Structurally, the pea/human class III enzymes are closely related, exhibiting a residue identity of 69% and with only 3 of 23 residues differing among those often considered in substrate and coenzyme binding. In contrast, the corresponding ethanol-active enzymes, the long-known human liver and pea alcohol dehydrogenases, differ more (47% residue identities) and are also in functionally important active site segments, with 12 of the 23 positions exchanged, including no less than 7 at the usually much conserved coenzyme-binding segment. These differences affect functionally important residues that are often class-distinguishing, such as those at positions 48, 51, and 115, where the plant ethanol-active forms resemble class III (Thr, Tyr, and Arg, respectively) rather than the animal ethanol-active class I forms (typically Ser, His, and Asp, respectively). Calculations of phylogenetic trees support the conclusions from functional residues in subgrouping plant ethanol-active dehydrogenases and the animal ethanol-active enzymes (class I) as separate descendants from the class III line. It appears that the classical plant alcohol dehydrogenases (now called class P) have a duplicatory origin separate from that of the animal class I enzymes and therefore a paralogous relationship with functional convergence of their alcohol substrate specificity. Combined, the results establish the conserved nature of class III also in plants, and contribute to the molecular and functional understanding of alcohol dehydrogenases by defining two branches of plant enzymes into the system.

Alcohol Dehydrogenase↗